A contemporary review of mechanical circulatory support
2014; Elsevier BV; Volume: 33; Issue: 7 Linguagem: Inglês
10.1016/j.healun.2014.02.014
ISSN1557-3117
AutoresChetan B. Patel, Jennifer Cowger, Andreas Zuckermann,
Tópico(s)Cardiac Arrest and Resuscitation
ResumoMechanical circulatory support has seen numerous advances in the recent years, with important observations made to guide patient selection for the therapy, indications for use, and management of devices after implantation. There is rapid growth in the use of left ventricular assist device therapy (LVAD) for advanced heart failure, with a movement to pursue device intervention earlier in the disease spectrum before comorbidities escalate. With this increase in LVAD use have come new challenges, including unanticipated adverse events and high readmission rates. Simultaneously, complications encountered during LVAD support and an increased number of patients supported with a goal for transplant have had an important effect on the allocation of cardiac allografts. Still, the field continues to evolve and address these challenges in systematic fashion to provide novel solutions and meet the needs of a growing population with advanced heart failure. This has led to an extensive body of literature, ranging from case reports to multicenter clinical trials, which will enhance the future of LVAD technology and patient outcomes. This review summarizes important publications in mechanical circulatory support during the past 24 months. Mechanical circulatory support has seen numerous advances in the recent years, with important observations made to guide patient selection for the therapy, indications for use, and management of devices after implantation. There is rapid growth in the use of left ventricular assist device therapy (LVAD) for advanced heart failure, with a movement to pursue device intervention earlier in the disease spectrum before comorbidities escalate. With this increase in LVAD use have come new challenges, including unanticipated adverse events and high readmission rates. Simultaneously, complications encountered during LVAD support and an increased number of patients supported with a goal for transplant have had an important effect on the allocation of cardiac allografts. Still, the field continues to evolve and address these challenges in systematic fashion to provide novel solutions and meet the needs of a growing population with advanced heart failure. This has led to an extensive body of literature, ranging from case reports to multicenter clinical trials, which will enhance the future of LVAD technology and patient outcomes. This review summarizes important publications in mechanical circulatory support during the past 24 months. Mechanical circulatory support (MCS) continues to evolve in device technology, patient selection, and long-term management of patients undergoing implantation of durable MCS systems. A larger number of patients worldwide are being considered for these therapies due to the growing experience with these devices and larger acceptance of implantation under the destination therapy (DT) indication. Commensurate with this expansion, societal organizations have developed and published guidelines regarding patient selection and device management. Many of these recommendations are based on findings from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which continues to provide data on our collective experience to date with MCS. In addition to these important publications, many other reports in 2012 to 2013 have highlighted the ongoing development of MCS as an important therapy in advanced heart failure. In this contemporary review, we summarize some of the most important articles published in the last 24 months. The fifth INTERMACS annual report provided data on nearly 7,000 patients receiving durable MCS devices in the United States (U.S.).1Kirklin J.K. Naftel D.C. Kormos R.L. et al.Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients.J Heart Lung Transplant. 2013; 32: 141-156Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar The number of implanting centers in the U.S. has continued to rise, demonstrating the staggering expansion of MCS as a therapeutic option for end-stage heart failure. The number of implanting centers in the U.S. increased from approximately 109 in January 2011 to 147 by January 2012, and 131 of these centers have approval for DT implants. Simultaneously, the INTERMACS report demonstrated a changing pattern in MCS intent, with an increasing number of patients (> 40% in the last report) now receiving an MCS implant under the DT indication. There are likely multiple reasons for this trend change, ranging from a fixed and limited donor pool for bridge to transplant (BTT) recipients, improved patient selection for left ventricular assist device (LVAD) therapy, an increase in the number of VAD implant centers, greater clinician and patient comfort with the concept of DT, and increased accessibility after regulatory approval for DT in many countries. Although device intent (BTT vs DT) is often assigned before durable LVAD implant, Tueteberg et al2Teuteberg J.J. Stewart G.C. Jessup M. et al.Implant strategies change over time and impact outcomes: insights from the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support).JCHF. 2013; 1: 369-378Google Scholar highlighted the dynamic nature of transplant candidacy during VAD support. In an analysis of 2,816 patients enrolled in INTERMACS, they showed that 43.5% of patients who were initially implanted with the BTT intent were no longer listed for cardiac transplantation at 2 years after implant. In contrast, nearly 15% of patients implanted as DT were being considered for transplant at the same time point. Not surprisingly, the most common pre-implant strategy (which remains unapproved by U.S. regulatory bodies) was bridge to candidacy (BTC). Implant strategy also forecasts patient outcome. The 2-year survivals of patients supported for BTT, BTC, and DT were 78% 70%, and 61%, respectively. Rapid changes in patient nutritional status, functional status, end-organ function, and adherence after LVAD can affect transplant candidacy and post-transplant survival, and the Tueteberg et al2Teuteberg J.J. Stewart G.C. Jessup M. et al.Implant strategies change over time and impact outcomes: insights from the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support).JCHF. 2013; 1: 369-378Google Scholar study highlights the need for continued efforts to reevaluate the dichotomous implant indications (BTT vs DT) we use in the current era. It also raises questions for VAD programs that specialize only in DT care, without an option for cardiac transplantation, and strategies of care in DT patients who may transition to transplant eligibility. Although the percentage of total LVAD implants defined a priori with BTT intent has decreased, MCS is playing a larger role in patients ultimately undergoing cardiac transplantation. The latest International Society for Heart and Lung Transplantation (ISHLT) Heart Report, which includes more than 3,529 adult transplants reported worldwide, indicates that nearly 30% of heart transplants were performed in adult patients supported by MCS, and the number continues to rise.3Lund L.H. Edwards L.B. Kucheryavaya A.Y. et al.The Registry of the International Society for Heart and Lung Transplantation: thirtieth official adult heart transplant report--2013; focus theme: age.J Heart Lung Transplant. 2013; 32: 951-964Abstract Full Text Full Text PDF PubMed Scopus (436) Google Scholar Post-transplant outcomes in BTT patients overall are improving with growing experience, particularly with long-term durable LVAD therapy.2Teuteberg J.J. Stewart G.C. Jessup M. et al.Implant strategies change over time and impact outcomes: insights from the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support).JCHF. 2013; 1: 369-378Google Scholar As such, studies show that MCS is having a larger effect on cardiac transplantation and the allocation process of organs in many U.S. centers and abroad. An analysis of the Scientific Registry of Transplant Recipients database found survival at 12 months in United Network of Organ Sharing (UNOS) status 1A listed patients was 75% in those with and 71% in those without VAD support and that transplants are now occurring more frequently in U.S. patients bridged with VAD support.4Colvin-Adams M. Smith J.M. Heubner B.M. et al.OPTN/SRTR 2011 Annual Data Report: heart.Am J Transplant. 2013; 13: 119-148Crossref PubMed Scopus (46) Google Scholar Columbia University Medical Center, one of the largest U.S. cardiac transplant centers, reported its experience with patients supported with long-term MCS and the effect of MCS on donor allocation.5Uriel N. Jorde U.P. Woo Pak S. et al.Impact of long term left ventricular assist device therapy on donor allocation in cardiac transplantation.J Heart Lung Transplant. 2013; 32: 188-195Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar Of the 726 adult heart transplants, 227 were bridged with MCS, and 164 (72%) received a transplant as UNOS 1A status. During a 6-year period, fewer patients received a transplant during their 1A grace period, and the number of BTT patients who received a transplant due to urgent 1A status for VAD complications increased from 43% to 86%.5Uriel N. Jorde U.P. Woo Pak S. et al.Impact of long term left ventricular assist device therapy on donor allocation in cardiac transplantation.J Heart Lung Transplant. 2013; 32: 188-195Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar Although multiple potential factors contribute to such trends, the increase in urgency statuses due to VAD complications is especially important in the context of data from the UNOS database that shows a 75% increase in mortality on the waiting list in patients whose status was upgraded because of LVAD-related complications.6Wever-Pinzon O. Drakos S.G. Kfoury A.G. et al.Morbidity and mortality in heart transplant candidates supported with mechanical circulatory support: is reappraisal of the current United network for organ sharing thoracic organ allocation policy justified?.Circulation. 2013; 127: 452-462Crossref PubMed Scopus (111) Google Scholar, 7Healy A.H. Baird B.C. Drakos S.G. Stehlik J. Selzman C.H. Impact of ventricular assist device complications on posttransplant survival: an analysis of the United Network of Organ Sharing database.Ann Thorac Surg. 2013; 95: 870-875Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Many advanced heart failure patients are reaping a survival benefit with the increased use of LVAD support, but important studies in 2013 highlighted sub-groups of heart failure patients with less success. Patients with biventricular failure demonstrate increased mortality after LVAD implant1Kirklin J.K. Naftel D.C. Kormos R.L. et al.Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients.J Heart Lung Transplant. 2013; 32: 141-156Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar and have reduced BTT6Wever-Pinzon O. Drakos S.G. Kfoury A.G. et al.Morbidity and mortality in heart transplant candidates supported with mechanical circulatory support: is reappraisal of the current United network for organ sharing thoracic organ allocation policy justified?.Circulation. 2013; 127: 452-462Crossref PubMed Scopus (111) Google Scholar and post-transplant survival.5Uriel N. Jorde U.P. Woo Pak S. et al.Impact of long term left ventricular assist device therapy on donor allocation in cardiac transplantation.J Heart Lung Transplant. 2013; 32: 188-195Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar Although rates of VAD use as BTT has significantly increased in those without congenital lesions, patients with congenital heart disease (CHD) have not enjoyed significant gains from MCS support. An analysis of UNOS data compared outcomes in 1,250 CHD patients listed for cardiac transplant vs outcomes in 59,606 listed patients without congenital lesions.8Gelow J.M. Song H.K. Weiss J.B. Mudd J.O. Broberg C.S. Organ allocation in adults with congenital heart disease listed for heart transplant: impact of ventricular assist devices.J Heart Lung Transplant. 2013; 32: 1059-1064Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar Whereas 18% of non-CHD adults in UNOS were listed on VAD support, this number represented only 3% of listed CHD patients. Further, mortality on the transplant list in VAD-supported patients was 26% in those without CHD compared with 41% in those with CHD.8Gelow J.M. Song H.K. Weiss J.B. Mudd J.O. Broberg C.S. Organ allocation in adults with congenital heart disease listed for heart transplant: impact of ventricular assist devices.J Heart Lung Transplant. 2013; 32: 1059-1064Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar The problem of allosensitization continues to be a challenge for listed patients supported with MCS technologies, and the problem is further confounded by improved technology to detect anti-human leukocyte antigen antibodies. Higher detection to date has not resulted in a clear signal toward increased rejection rates or allograft failure.9Shankar N. Daly R. Geske J. et al.LVAD implant as a bridge to heart transplantation is associated with allosensitization as measured by single antigen bead assay.Transplantation. 2013; 96: 324-330Crossref PubMed Scopus (33) Google Scholar Multicenter studies have demonstrated a continued improvement in outcomes with durable MCS. The greatest survival gains are reported in patients implanted under the DT indication with a HeartMate II axial-flow device (Thoratec Corp, Pleasanton, CA),10Park S.J. Milano C.A. Tatooles A.J. et al.Outcomes in advanced heart failure patients with left ventricular assist devices for destination therapy.Circ Heart Fail. 2012; 5: 241-248Crossref PubMed Scopus (270) Google Scholar mainly because of the inferior survival in the early DT experience. The BTT HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) study compared outcomes in 140 BTT patients undergoing a HeartWare HVAD (HeartWare International Inc, Framingham, MA) implant with 499 patients in a contemporaneous control group from INTERMACS11Aaronson K.D. Slaughter M.S. Miller L.W. et al.Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation.Circulation. 2012; 125: 3191-3200Crossref PubMed Scopus (495) Google Scholar who were largely supported with the HeartMate II. Survival rates at 1 year were 90.7% in the HVAD group and 90.1% in control group, leading to U.S. Food and Drug Administration approval of the HeartWare HVAD for BTT candidates and an expansion of HVAD indications beyond European borders. The results of the ENDURANCE study, which compared outcomes in DT patients supported with the HeartWare vs the present industry DT leader—the HeartMate II LVAD—are eagerly awaited and are expected to be available in 2014. Despite improving outcomes, efforts to refine patient risk assessment and selection for MCS continue to be a theme of MCS research. There was renewed interest in use of echocardiographic parameters to assess risk for right ventricular (RV) failure after durable LVAD therapy. Investigators at Cleveland Clinic used quantitative measures of RV function to assess risk of RV failure by echocardiography. Patients requiring an RVAD or prolonged inotropic support (> 14 days) were more likely to have reduced RV free wall strain by echocardiographic vector velocity imaging. A peak strain cutoff of –9.6% was associated with the highest sensitivity and specificity to predict RV failure. Moreover, incorporating RV strain was incremental to the previously reported scores for RV failure.12Grant A.D.M. Smedira N.G. Starling R.C. Marwick T.H. Independent and incremental role of quantitative right ventricular evaluation for the prediction of right ventricular failure after left ventricular assist device implantation.J Am Coll Cardiol. 2012; 60: 521-528Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar A complementary study examining the comparative size of the RV and LV in 109 patients showed that an RV-to-LV diameter ratio > 0.75 was predictive of RV failure after LVAD implantation.13Vivo R.P. Cordero-Reyes A.M. Qamar U. et al.Increased right-to-left ventricle diameter ratio is a strong predictor of right ventricular failure after left ventricular assist device.J Heart Lung Transplant. 2013; 32: 792-799Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar This variable also added incremental value to other scores, including those that included hemodynamic variables. Global risk scores also remain of interest with the expansion of therapy, especially in older individuals. Using the HeartMate II clinical trials database of 1,122 patients, Cowger et al14Cowger J. Sundareswaran K. Rogers J.G. et al.Predicting survival in patients receiving continuous flow left ventricular assist devices: the HeartMate II risk score.J Am Coll Cardiol. 2013; 61: 313-321Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar developed the most comprehensive global risk score to date for patients being considered for continuous-flow technology. Components of the Heart Mate II multivariable risk score (HMRS) included age (decade), serum albumin (mg/dl), serum creatinine (mg/dl), international normalized ratio (INR), and implanting center volume (increasing risk with annual center volume < 15).14Cowger J. Sundareswaran K. Rogers J.G. et al.Predicting survival in patients receiving continuous flow left ventricular assist devices: the HeartMate II risk score.J Am Coll Cardiol. 2013; 61: 313-321Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar An application for mobile devices is available for score calculation (https://itunes.apple.com/us/app/lvad-calc/id773254190?ls=1&mt=8). The score can be used to estimate patient mortality after VAD implant and may be an important patient tool for the informed consent process. Older risk scores were also tested in an era with modern surgical techniques, improved patient selection, and continuous-flow devices. The Lietz-Miller Destination Therapy Risk Score (DTRS), derived from a HeartMate XVE cohort, was analyzed in more than 1,000 patients supported with the HeartMate II device and only had modest discriminatory value for DT patients treated with continuous-flow LVADs.15Teuteberg J.J. Ewald G.A. Adamson R.M. et al.Risk assessment for continuous flow left ventricular assist devices: does the destination therapy risk score work? An analysis of over 1,000 patients.J Am Coll Cardiol. 2012; 60: 44-51Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Finally, scores developed to assess non-cardiac organ function were also applied to the MCS field to assess post-implant outcomes. The model of end-stage liver disease (MELD) was shown to be a predictor of adverse events in INTERMACS,16Matthews J.C. Pagani F.D. Haft J.W. Koelling T.M. Naftel D.C. Aaronson K.D. Model for end-stage liver disease score predicts left ventricular assist device operative transfusion requirements, morbidity, and mortality.Circulation. 2010; 121: 214-220Crossref PubMed Scopus (160) Google Scholar and findings were validated by Yang et al17Yang J.A. Kato T.S. Shulman B.P. et al.Liver dysfunction as a predictor of outcomes in patients with advanced heart failure requiring ventricular assist device support: use of the Model of End-stage Liver Disease (MELD) and MELD eXcluding INR (MELD-XI) scoring system.J Heart Lung Transplant. 2012; 31: 601-610Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar in a study of 200 patients. The MELD score and Heart Mate II risk score have similar score components and neither was superior in direct comparison.14Cowger J. Sundareswaran K. Rogers J.G. et al.Predicting survival in patients receiving continuous flow left ventricular assist devices: the HeartMate II risk score.J Am Coll Cardiol. 2013; 61: 313-321Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar Nevertheless, both risk models emphasize the need (as in other global scores) for a careful evaluation of extracardiac function in the pre-operative setting. The study of short-term MCS in the past year provided important insight into the heterogenous nature of cardiogenic shock and the need for carefully designed future studies in this realm. The intraaortic balloon pump (IABP) SHOCK-II trial examined the use of an IABP in cardiogenic shock complicating acute myocardial infarction. This prospective study randomized 600 patients to IABP therapy or usual care at the time of anticipated revascularization. Surprisingly, IABP therapy was not associated with reduced 30-day mortality.18Thiele H. Zeymer U. Neumann F.J. et al.Intraaortic balloon support for myocardial infarction with cardiogenic shock.N Engl J Med. 2012; 367: 1287-1296Crossref PubMed Scopus (1491) Google Scholar Given the moderate-risk nature of the randomized cohort, O'Connor and Rogers19O'Connor C.M. Rogers J.G. Evidence for overturning the guidelines in cardiogenic shock.N Engl J Med. 2012; 367: 1349-1350Crossref PubMed Scopus (29) Google Scholar suggested these results should lead to a reevaluation of our understanding and subsequent therapeutic strategies in cardiogenic shock, with a need to readdress our current indications for device support. Use of this decades-old technology has subsequently been explored in a slightly different population: chronic heart failure progressing to cardiogenic shock.19O'Connor C.M. Rogers J.G. Evidence for overturning the guidelines in cardiogenic shock.N Engl J Med. 2012; 367: 1349-1350Crossref PubMed Scopus (29) Google Scholar Estep et al20Estep J.D. Cordero-Reyes A.M. Bhimaraj A. et al.Percutaneous placement of an intra-aortic balloon pump in the left axillary/subclavian position provides safe, ambulatory long-term support as bridge to heart transplant.JCHF. 2013; 1: 382-388Google Scholar described an experience of extended IABP support (median support time, 18 days; range, 4–152 days) from a percutaneous axillary approach in 50 patients as a BTT. Not only did this expand the use of this device, which has been in clinical practice for many years, but this study also reported a novel insertion method that would allow ambulation in the end-stage heart failure patient. Although myocardial recovery with a variety of long-term and short-term MCS devices has been reported, overall rates of myocardial recovery with long term MCS devices remain very low.1Kirklin J.K. Naftel D.C. Kormos R.L. et al.Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients.J Heart Lung Transplant. 2013; 32: 141-156Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar There have been some interesting insights into this low rate, including the assessment of myocardial samples after prolonged MCS and the use of plasma biomarkers. Not all patients treated with durable LVAD have a decrease in markers of extracellular matrix proteins, such as the matrix metalloproteinases, and persistent elevation in these markers may result in RV failure.21Kato T.S. Chokshi A. Singh P. et al.Markers of extracellular matrix turnover and the development of right ventricular failure after ventricular assist device implantation in patients with advanced heart failure.J Heart Lung Transplant. 2012; 31: 37-45Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Similarly, galectin-3, a novel heart failure biomarker that is associated with myocardial fibrosis, was examined in peripheral blood samples with concomitant measurement of myocardial messenger RNA in patients undergoing MCS. Galectin-3 levels remained elevated after MCS and predicted worse outcomes with higher levels.22Erkilet G. Ozpeker C. Bothig D. et al.The biomarker plasma galectin-3 in advanced heart failure and survival with mechanical circulatory support devices.J Heart Lung Transplant. 2013; 32: 221-230Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Collectively, these data suggest there may be novel targets for therapies beyond neurohormonal antagonists to treat heart failure as an adjunct to MCS support. In addition to fully understanding the recovery process, studies have challenged the methods and frequency with which we assess for improved myocardial function. Investigators from the Utah Cardiac Recovery Program assessed myocardial recovery by using a protocol-driven echocardiographic assessment in ischemic and non-ischemic cardiomyopathy and showed evidence of recovery as early as 30 days after LVAD implantation, with the greatest effect seen at 6 months.23Drakos S.G. Wever-Pinzon O. Selzman C.H. et al.Magnitude and time course of changes induced by continuous-flow left ventricular assist device unloading in chronic heart failure: insights into cardiac recovery.J Am Coll Cardiol. 2013; 61: 1985-1994Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar The greatest improvement was in younger patients with the shortest duration of heart failure, and these finding were consistent with other studies.24Goldstein D.J. Maybaum S. MacGillivray T.E. et al.Young patients with nonischemic cardiomyopathy have higher likelihood of left ventricular recovery during left ventricular assist device support.J Card Fail. 2012; 18: 392-395Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar However, the results suggest that some recovery is possible in a larger proportion of patients with mechanical unloading and that further investigation will be required to see how much recovery is adequate for LVAD explant. The growing population of patients supported by durable MCS devices has had an important effect on the infrastructure required to manage patients outside of the implanting hospital and on costs to the health care system. Single-center studies have reported readmission rates after LVAD implantation between 1.5 and 2.5 per patient-year of support, with an increased rate in the first 6 months after implant.25Hasin T. Marmor Y. Kremers W. et al.Readmissions after implantation of axial flow left ventricular assist device.J Am Coll Cardiol. 2013; 61: 153-163Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 26Forest S.J. Bello R. Friedmann P. et al.Readmissions after ventricular assist device: etiologies, patterns, and days out of hospital.Ann Thorac Surg. 2013; 95: 1276-1281Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 27Smedira N.G. Hoercher K.J. Lima B. et al.Unplanned hospital readmissions after HeartMate II implantationfrequency, risk factors, and impact on resource use and survival.JCHF. 2013; 1: 31-39Google Scholar The leading cause for readmission was bleeding (primarily gastrointestinal), followed by heart failure/arrhythmia and then infection.25Hasin T. Marmor Y. Kremers W. et al.Readmissions after implantation of axial flow left ventricular assist device.J Am Coll Cardiol. 2013; 61: 153-163Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Gastrointestinal bleeding due to development of arteriovenous malformations remains common after implantation of continuous-flow devices and is believed to be due to reduced pulse pressure. For the first time, the survival effect of this most common adverse event was reported by the group at Henry Ford Hospital, who demonstrated that although gastrointestinal bleeding is a common morbidity associated with LVAD therapy, survival was not negatively affected.28Morgan J.A. Paone G. Nemeh H.W. et al.Gastrointestinal bleeding with the HeartMate II left ventricular assist device.J Heart Lung Transplant. 2012; 31: 715-718Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar In an effort to reduce events, investigators also showed that increased pulsatility is associated with reduced bleeding events, setting the stage for a possible prospective study examining different unloading strategies during continuous-flow device support.29Wever-Pinzon O. Selzman C.H. Drakos S.G. et al.Pulsatility and the risk of nonsurgical bleeding in patients supported with the continuous-flow left ventricular assist device HeartMate II.Circ Heart Fail. 2013; 6: 517-526Crossref PubMed Scopus (172) Google Scholar On the opposing side of the bleeding-thrombosis paradigm, there was emerging interest in understanding the risk of thrombosis and associated phenomena such as hemolysis. A multicenter study of 837 patients undergoing HeartMate II implant between 2004 and 2013 documented 72 device thromboses in 66 patients.30Starling R.C. Moazami N. Silvestry S.C. et al.Unexpected abrupt increase in left ventricular assist device thrombosis.N Engl J Med. 2014; 370: 33-40Crossref PubMed Scopus (604) Google Scholar Importantly, the authors showed a time-related increase in LVAD thrombosis. The occurrence of confirmed device thrombosis within 3 months of device implant increased from 2.2% (95% confidence interval [CI], 1.5%–3.4%) in patients implanted in March 2011 to 8.4% (95% CI, 5.0%–13.9%) in those implanted in January 2013. Further, median times to device thrombosis from implant decreased from 18.6 months (95% CI, 0.5–53 months) for HeartMate II implants before March 2011 to 2.7 months for implants thereafter. Several studies have identified better means of detecting device thrombosis and risk factors for thrombosis development. Cowger et al,31Shah P. Mehta V.M. Cowger J.A. et al.Lactate dehydrogenase is superior to serum free hemoglobin as a marker of pump thrombosis in left ventricular assist devices.J Heart Lung Transplant. 2013; 32: S37Abstract Full Text PDF Google Scholar with the University of Michigan group, showed that the current INTERMACS definition for hemolysis and thrombosis using a serum free hemoglobin > 40 mg/dl la
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