Carol Chen, MD

All Publications

• Transplant Volume Is Associated With Graft Acceptance Threshold and Center Resource Availability. Journal of cardiac failure Chen, C. W., Auvil, B. J., Zhang, J. C., Chung, J. J., Gaffey, A. C., Bermudez, C. A., Goldberg, L. R., Acker, M. A., Atluri, P. 2020; 26 (6): 522-526

  Abstract

  Heart transplant volume varies significantly among centers. We hypothesized that centers where the transplant team routinely accepts organs previously declined by other centers and where operating room availability is unrestricted have higher transplant volumes.We used the potential transplant recipient sequence number in the United Network for Organ Sharing database as a surrogate for graft acceptance threshold and the number of transplantations occurring on weekends and 8 major holidays as a marker of center resource availability. Centers were classified as low-, medium-, or high-volume if the average annual number of transplants were, respectively, <10, 10-30, or >30 over a 10-year period. From July 12, 2006, to December 31, 2015, 19,054 transplants were performed by 142 centers. There were 59 low-volume centers, 69 medium-volume centers, and 14 high-volume centers with median potential transplant recipient sequence numbers for transplanted candidates of 7 (interquartile range 3-11), 7 (5-10), and 15 (7-40), respectively (P = .002). The median proportion of off-hours transplantations performed by medium-volume centers was 28% (25%-31%) compared with 32% (29%-33%) by high-volume centers (P = .009). Five-year survival was equivalent among all centers (P = .053).Transplants for candidates with high sequence numbers and unrestricted operating room availability are associated with increased center volume without sacrificing post-transplantation survival.

  View details for DOI 10.1016/j.cardfail.2019.03.009

  View details for PubMedID 30898599

• Interaction of Donor and Recipient Age: Do Older Heart Transplant Recipients Require Younger Hearts? The Annals of thoracic surgery Daniel, M., Chen, C., Chung, J., Goldberg, L., Acker, M. A., Atluri, P. 2019; 107 (1): 62-66

  Abstract

  Older patients (aged 60 years or more) awaiting heart transplant often have comorbidities that may limit overall survival independent of cardiac status. We hypothesized that these comorbidities have a more-limiting impact on survival than age of donor heart and that older allografts might be utilized in these patients without compromising outcomes.We identified all transplant recipients aged more than 60 years in the United Network for Organ Sharing database. Local regression analysis detected the point above which increasing donor age incurred increasing risk of mortality, above and below which two cohorts were defined. Kaplan-Meier analysis compared cumulative 5-year survival between groups. Cox proportional hazard modeling was then used to determine the hazards of death in the two groups.An inflection point in posttransplant survival was detected near donor age 50 years. Of 14,113 older recipients studied, 86% received younger donor hearts (less than 50 years of age), and 14% received advanced age allografts (50 years of age or more). Baseline characteristics were comparable between groups except more recipients had left ventricular assist devices at time of transplant in the younger donor group (15% versus 9%, p < 0.001). Five-year survival was significantly lower among recipients receiving advanced age hearts compared with those receiving younger hearts (67% versus 73%, log rank p < 0.001). Adjusting for relevant recipient baseline characteristics, patients receiving advanced age hearts were 30% more likely to die by 5 years compared with patients receiving younger hearts.Transplant recipients aged 60 years and more who receive advanced age donor hearts (50 years or more) have a significantly increased risk of mortality. With careful allograft selection, use of donor hearts to age 50 may be acceptable among older transplant recipients.

  View details for DOI 10.1016/j.athoracsur.2018.06.085

  View details for PubMedID 30172858

• Preoperative renal dysfunction does not affect outcomes of left ventricular assist device implantation. The Journal of thoracic and cardiovascular surgery Kilic, A., Chen, C. W., Gaffey, A. C., Wald, J. W., Acker, M. A., Atluri, P. 2018; 156 (3): 1093-1101.e1

  Abstract

  Selection criteria for durable left ventricular assist device (LVAD) implantation remain unclear. One such criterion is renal function. In this study we evaluated outcomes of LVAD implantation in patients with preoperative renal dysfunction.Patients with implanted LVADs as destination therapy (DT) or bridge to transplantation (BTT) at a single institution between 2006 and 2015 were included. Primary stratification was according to pre-implantation glomerular filtration rate (GFR): >60 mL/min versus <60 mL/min or dialysis dependence. The primary outcome was post-LVAD implantation overall survival.Two hundred thirty-eight patients underwent LVAD implantation during the study period as DT (60%; n = 142) or BTT (40%; n = 96). Reduced GFR was present in 56% (n = 132), with 8% (n = 18) being dialysis-dependent. Normal versus reduced GFR cohorts were well matched except for a higher incidence of coronary artery disease in the patients with reduced GFR (61% vs 48%; P = .04). Mean follow-up was 13.5 ± 17.0 months. Unadjusted and risk-adjusted survival at 1, 3, 6, and 12 months after LVAD implantation were similar between the cohorts for DT and BTT. Rates of transplantation were comparable in BTT patients (61% normal vs 53% reduced GFR; P = .43). Recovery of renal function to a GFR >60 mL/min occurred in 43% (n = 17) and 57% (n = 42) of patients with reduced GFR in the BTT and DT cohorts, respectively, by 1 year post implantation.Well selected patients with preexisting renal dysfunction can undergo LVAD implantation with acceptable outcomes. Approximately half of LVAD recipients with preimplantation renal dysfunction will recover normal renal function within the first postoperative year. Renal dysfunction alone should not serve as an absolute contraindication to LVAD therapy.

  View details for DOI 10.1016/j.jtcvs.2017.12.044

  View details for PubMedID 30017440

• Sustained release of endothelial progenitor cell-derived extracellular vesicles from shear-thinning hydrogels improves angiogenesis and promotes function after myocardial infarction. Cardiovascular research Chen, C. W., Wang, L. L., Zaman, S., Gordon, J., Arisi, M. F., Venkataraman, C. M., Chung, J. J., Hung, G., Gaffey, A. C., Spruce, L. A., Fazelinia, H., Gorman, R. C., Seeholzer, S. H., Burdick, J. A., Atluri, P. 2018; 114 (7): 1029-1040

  Abstract

  Previous studies have demonstrated improved cardiac function following myocardial infarction (MI) after administration of endothelial progenitor cells (EPCs) into ischaemic myocardium. A growing body of literature supports paracrine effectors, including extracellular vesicles (EVs), as the main mediators of the therapeutic benefits of EPCs. The direct use of paracrine factors is an attractive strategy that harnesses the effects of cell therapy without concerns of cell engraftment or viability. We aim to reproduce the beneficial effects of EPC treatment through delivery of EPC-derived EVs within a shear-thinning gel (STG) for precise localization and sustained delivery.EVs were harvested from EPCs isolated from adult male Rattus norvegicus (Wistar) rats and characterized by electron microscopy, nanoparticle tracking analysis (NTA), and mass spectrometry. EVs were incorporated into the STG and injected at the border zone in rat models of MI. Haemodynamic function, angiogenesis, and myocardial remodelling were analyzed in five groups: phosphate buffered saline (PBS) control, STG control, EVs in PBS, EVs in STG, and EPCs in STG. Electron microscopy and NTA of EVs showed uniform particles of 50-200 nm. EV content analysis revealed several key angiogenic mediators. EV uptake by endothelial cells was confirmed and followed by robust therapeutic angiogenesis. In vivo animal experiments demonstrated that delivery of EVs within the STG resulted in increased peri-infarct vascular proliferation, preservation of ventricular geometry, and improved haemodynamic function post-MI.EPC-derived EVs delivered into ischaemic myocardium via an injectable hydrogel enhanced peri-infarct angiogenesis and myocardial haemodynamics in a rat model of MI. The STG greatly increased therapeutic efficiency and efficacy of EV-mediated myocardial preservation.

  View details for DOI 10.1093/cvr/cvy067

  View details for PubMedID 29566124

  View details for PubMedCentralID PMC5967544

• Is there a difference in bleeding after left ventricular assist device implant: centrifugal versus axial? Journal of cardiothoracic surgery Gaffey, A. C., Chen, C. W., Chung, J. J., Han, J., Bermudez, C. A., Wald, J., Atluri, P. 2018; 13 (1): 22

  Abstract

  Continuous-flow left ventricular assist devices (CF-LVAD) have become the standard of care for patients with end stage heart failure. Device reliability has increased, bringing the potential for VAD, compared to transplant, into debate. However, complications continue to limit VADs as first line therapy. Bleeding is a major morbidity. A debate exists as to the difference in bleeding profile between the major centrifugal and axial flow devices. We hypothesized that there would be similar adverse bleeding event profiles between the 2 major CF-LVADs.We retrospectively investigated isolated CF LVADs performed at our institution between July 2010 and July 2015: HeartMateII (HMII, n = 105) and HeartWare (HVAD, n = 34). We reviewed demographic, perioperative and short- and long-term outcomes.There was no significant difference in demographics or comorbidities. There was a low incidence of gastrointestinal (GI) bleed 3.9% in HMII and 2.9% in HVAD (p = 0.78). Preoperatively, the cohorts did not differ in coagulation measures (p = 0.95). Within the post-operative period, there was no difference in product transfusion: red blood cells (p = 0.10), fresh frozen plasma (p = 0.19), and platelets (p = 0.89). Post-operatively, a higher but not significantly different number of HMII patients returned to the operating room for bleeding (n = 27) compared to HVAD (n = 6, p = 0.35). There was no difference in rates of stroke (p = 0.65), re-intubation (p = 0.60), driveline infection (p = 0.05), and GI bleeding (p = 0.31). The patients had equivalent ICU LOS (p = 0.86) and index hospitalization LOS (p = 0.59).We found no difference in the rate of bleeding complications between the current commercially available axial and centrifugal flow devices.

  View details for DOI 10.1186/s13019-018-0703-z

  View details for PubMedID 29433532

  View details for PubMedCentralID PMC5810067

• Improved Approach With Subcostal Exchange of the HeartMate II Left Ventricular Assist Device: Difference in On and Off Pump? The Annals of thoracic surgery Gaffey, A. C., Chen, C. W., Chung, J. J., Phillips, E., Wald, J., Williams, M. L., Low, D. W., Acker, M. A., Atluri, P. 2017; 104 (5): 1540-1546

  Abstract

  The HeartMate II (St. Jude Medical, Inc, St. Paul, MN [previously Thoratec]) left ventricular assist device (LVAD) exchange has traditionally involved a redo sternotomy. Alternate minimally invasive subcostal approaches have the advantage of avoiding sternal reentry, excessive bleeding, and prolonged recovery.This retrospective review included patients who underwent an exchange from May 2009 to March 2016. The patients were divided into three cohorts: (1) redo sternotomy, (2) subcostal approach involving cardiopulmonary bypass (CPB) (ON-CPB SC), and (3) subcostal approach off the CPB pump (OFF-CPB SC). Data pertaining to patients' baseline characteristics and outcomes were collected and analyzed.From May 1, 2009 to July 31, 2016, 33 HeartMate II LVAD exchanges were performed. There were 11 redo sternotomies and 22 subcostal exchanges, 12 of which were in the OFF-CPB SC group. There was no significant difference among the groups in terms of age (p = 0.75), sex (p = 0.95), and indication for exchange (p = 0.94). There was a higher red blood cell transfusion requirement within the sternotomy cohort (p < 0.001). The median time to extubation and the intensive care unit length of stay were significantly shorter in the OFF-CPB SC group (1 and 2.5 days, respectively) than in the sternotomy (2.5 and 21 day, respectively) and ON-CPB SC groups (1.5 and 5 days, respectively). The 30-day and 90-day survival rates were equivalent among the cohorts.Exchange of the HeartMate II LVAD can be accomplished with significantly improved recovery time and transfusion requirement through a less invasive subcostal approach when compared with sternotomy. The subcostal approach can be performed safely both on and off cardiopulmonary bypass.

  View details for DOI 10.1016/j.athoracsur.2017.04.047

  View details for PubMedID 28760470

• Extended distance cardiac allograft can successfully be utilized without impacting long-term survival. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Gaffey, A. C., Chen, C. W., Chung, J. J., Han, J., Owens, A., Acker, M. A., Atluri, P. 2017; 36 (9): 968-972

  Abstract

  Despite the severe shortage of donor cardiac allografts, the general belief in worse outcomes with donors from prolonged distances has resulted in many centers greatly limiting the acceptable geographic distance of acceptable donors. However, with improvements in allograft preservation, it is likely that distance may be extended without compromising graft integrity. We hypothesized that recipients of appropriately selected allografts from greater distances would have equivalent long-term survival compared with recipients from closer geographic regions.We retrospectively analyzed the United Network for Organ Sharing (UNOS) adult heart transplant data from January 2000 to December 2013. Recipients were stratified by donor distance. Demographic and outcomes data were analyzed, with a primary end-point of survival.During the study period, 25,996 isolated orthotopic heart transplantations (OHTs) were performed. Patients were stratified by distance: 0 to 500 miles (n = 24,645); 501 to 1,000 miles (n = 1,201); 1,001 to 1,500 miles (n = 134); and 1,501+ miles (n = 16). Increased donor allograft distance correlated with significantly longer ischemic times (3.1 miles for 0 to 500 miles vs 7.5 hours for 1,501+ miles, p = 0.0001). One- and 5-year survival was similar in all cohorts, using Kaplan-Meier survival analysis (log rank, p = 0.8025). There was no difference in rate of stroke (p = 0.82), dialysis (p = 0.60) or reoperation (p = 0.28). Length of stay was equivalent across cohorts (p = 0.11).Appropriately selected allografts from donors at a greater distance should be considered to increase organ availability. Donor heart procurement from increased distance may not directly increase morbidity and mortality post-heart transplant.

  View details for DOI 10.1016/j.healun.2017.04.002

  View details for PubMedID 28457697

• Non-cardiac surgery in patients with continuous-flow left ventricular assist devices: a single institutional experience. Journal of investigative medicine : the official publication of the American Federation for Clinical Research Chen, C. W., Dumon, K. R., Shaked, O., Acker, M. A., Atluri, P., Dempsey, D. T. 2017; 65 (5): 912-918

  Abstract

  With improvements in life expectancy for patients with continuous-flow left ventricular assist devices (LVADs), non-cardiac surgeons will increasingly encounter surgical problems in this population. 209 patients underwent LVAD placement between 10/1/2007 and 6/1/2015 at a single institution. Survival was compared between patients who had non-cardiac surgery (NCS) during the initial LVAD implantation hospitalization (n=36) and those who had NCS only in subsequent hospitalizations (n=33). Postoperative complication rates were examined. Index admission NCS was associated with lower 5-year survival compared with subsequent admission NCS (27.1% vs 39.4%, p=0.017). In subsequent admissions, the risks of bleeding and infectious complications were the same for elective or urgent NCS, but the risk of death was higher in the urgent surgery group. We conclude that elective NCS can be performed with low risk of death or LVAD dysfunction after sufficient recovery of patients from LVAD implantation.

  View details for DOI 10.1136/jim-2016-000297

  View details for PubMedID 28341625

• Low ejection fraction in donor hearts is not directly associated with increased recipient mortality. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Chen, C. W., Sprys, M. H., Gaffey, A. C., Chung, J. J., Margulies, K. B., Acker, M. A., Atluri, P. 2017; 36 (6): 611-615

  Abstract

  Reduced left ventricular ejection fraction (EF) in the donor heart is often a contraindication for transplant. However, small studies have validated the use of hearts with evidence of myocardial dysfunction to boost the number of organs available for transplant. We hypothesize that donor hearts with reduced EF undergo myocardial recovery after transplant and result in equivalent recipient survival compared with grafts with normal function.We examined post-operative outcomes of heart recipients in the database of the United Network for Organ Sharing. Patients were grouped by donor EF as follows: <40% (reduced EF); between 40% and 50% (borderline EF); and ≥50% (normal EF). Propensity score matching was performed to compare separately reduced and borderline EF patients with normal EF patients.Of 30,993 donors from 1996 to 2015, 127 (0.4%) had reduced EF, 613 (2.0%) had borderline EF and 30,253 (97.6%) had normal EF. In each of the 2 propensity score comparisons, the odds of post-operative stroke (p = 0.139, p = 0.551), pacemaker requirement (p = 0.238, p = 0.739), primary graft failure (p = 0.569, p = 0.817), rejection (p = 0.376, p = 0.533) and death at 1 year (p = 0.124, p = 0.247) were equivalent. At roughly 1-year follow-up after transplant, the mean EF of the reduced EF group was 58.0 ± 10.3% compared with 59.5 ± 7.5% in the matched normal EF group (p = 0.289). The mean follow-up EF of the borderline EF group was 58.3 ± 9.1% compared with 59.3 ± 7.7% in the matched normal EF group (p = 0.106).Recipients of hearts with reduced EF have equivalent 1-year survival compared with recipients of hearts with normal EF. Donor hearts with reduced EF show significant functional recovery after transplant.

  View details for DOI 10.1016/j.healun.2017.02.001

  View details for PubMedID 28314504

• Bridge with a left ventricular assist device to a simultaneous heart and kidney transplant: Review of the United Network for Organ Sharing database. Journal of cardiac surgery Gaffey, A. C., Chen, C. W., Chung, J., Grandin, E. W., Porrett, P. M., Acker, M. A., Atluri, P. 2017; 32 (3): 209-214

  Abstract

  Left ventricular assist device (LVAD) implantation as a bridge to cardiac transplantation (BTT) is an effective treatment for end-stage heart failure patients. Currently, there is an increasing number of patients with a LVAD who need a heart and kidney transplant (HKT). Little is known of the prognostic outcomes in these patients. This study was undertaken to determine whether an equivalent outcome would be present in HKTs as compared to a non-LVAD primary HKT cohort.We reviewed the United Network for Organ Sharing database from 2004 to 2013. Orthotropic heart transplant recipients (n = 49 799) were subcategorized as dual organ HKT (n = 1 921) and then divided into cohorts of HKT following continuous flow left ventricular assist device placement (CF-VAD-HKT, n = 113) or no LVAD placement (HKT, n = 1 808). Survival after transplantation was analyzed.For CF-LVAD-HKT and HKT cohorts, preoperative characteristics were similar regarding age (50.8 ± 13.7, 50.1 ± 13.7, p = 0.75) and panel reactive antibody (12.3 ± 18.4 vs 7.1 ± 18.4, p = 0.06). Donors were similar in age, gender, creatinine, and ejection fraction. Post-transplant, there was no difference in complications. Survival for CF-LVAD-HKT and HKT were similar at 1 year (77% vs 82%) and 3 years (75% vs 77%, log rank p = 0.2814).For patients with advanced heart failure and persistent renal dysfunction, simultaneous HKT is a safe option. Survival after CF-LVAD-HKT is equivalent to conventional HKT.

  View details for DOI 10.1111/jocs.13105

  View details for PubMedID 28176387