Publications by authors named "Lawrence Czer"

111 Publications

Long-term outcomes after heart transplantation using ex vivo allograft perfusion in standard risk donors: A single-center experience.

Clin Transplant 2022 Jan 14:e14591. Epub 2022 Jan 14.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Introduction: The Organ Care System (OCS) is an ex vivo perfusion platform for donor heart preservation. Short/mid-term post-transplant outcomes after its use are comparable to standard cold storage (CS). We evaluated long-term outcomes following its use.

Methods: Between 2011 and 2013, 38 patients from a single center were randomized as a part of the PROCEED II trial to receive allografts preserved with CS (n = 19) or OCS (n = 19). Endpoints included 8-year survival, survival free from graft-related deaths, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejections.

Results: Eight-year survival was 57.9% in the OCS group and 73.7% in the CS group (p = .24). Freedom from CAV was 89.5% in the OCS group and 67.8% in the CS group (p = .13). Freedom from NF-MACE was 89.5% in the OCS group and 67.5% in the CS group (p = .14). Eight-year survival free from graft-related death was equivalent between the two groups (84.2% vs. 84.2%, p = .93). No differences in rejection episodes were observed (all p > .5).

Conclusions: In select patients receiving OCS preserved allografts, late post-transplant survival trended lower than those transplanted with an allograft preserved with CS. This is based on a small single-center series, and larger numbers are needed to confirm these findings.
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http://dx.doi.org/10.1111/ctr.14591DOI Listing
January 2022

Diagnosing heparin-induced thrombocytopenia in mechanical circulatory support device patients.

J Heart Lung Transplant 2022 Jan 17;41(1):80-85. Epub 2021 Sep 17.

Pathology, Cedars Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Mechanical circulatory support device (MCSD) patients with positive heparin-induced thrombocytopenia (HIT) screening pose a unique challenge, as clinicians must make rapid decisions about their anticoagulation and whether they can safely undergo cardiopulmonary bypass. We identified screening practices at our institution and other institutions nationwide that differed from American Society of Hematology (ASH) guidelines. This discovery prompted a data review to confirm the applicability of guidelines to this unique population and to highlight complications of "gestalt" screening.

Methods: Our study included MCSD patients with HIT testing from April 2014 to August 2020. We evaluated 510 PF4 IgG ELISA results.

Results: HIT was confirmed in 4.2% of patients. There was an increased prevalence of HIT in patients with nondurable (5.3%) vs durable devices (2.9%) or those in the preimplantation setting (1.3%), however this difference was not statistically significant (p = 0.26). None of the patients with a low probability 4T Score had HIT. All patients with a high probability 4T Score and PF4 immunoassay OD >2.0 had HIT. False positive results occurred in 22% of assays ordered for patients with a low probability 4T Score. Twelve patients with a low probability 4T Score and a false positive immunoassay were switched to a direct thrombin inhibitor (DTI) while awaiting confirmatory results. Two patients experienced clinically significant bleeding after conversion to a DTI. An organ was refused in one patient with false positive HIT screening.

Conclusions: Our findings demonstrate that an opportunity exists to improve clinical outcomes by re-emphasizing the utility of established guidelines and highlighting their safe use in the MCSD patient population.
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http://dx.doi.org/10.1016/j.healun.2021.09.006DOI Listing
January 2022

The effects of donor-specific antibody characteristics on cardiac allograft vasculopathy.

Clin Transplant 2021 Dec 28;35(12):e14483. Epub 2021 Oct 28.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Cardiac allograft vasculopathy (CAV) causes late graft dysfunction and post-transplant mortality. Currently, the effects of different donor-specific antibodies (DSA) on the severity of CAV remain unclear.

Method: We evaluated 526 adult heart transplant recipients at a single center between January 2010 and August 2015. Subjects were divided into those with DSA (n = 142) and those without DSA (n = 384, control). The DSA group was stratified into persistent DSA (n = 34), transient DSA (n = 105), 1:8 dilution DSA (n = 45), complement-binding (C1q) DSA (n = 36), Class I DSA (n = 37), and Class II DSA (n = 105). The primary outcome was the incidence of moderate-to-severe CAV (CAV 2/3) at 5-year follow-up.

Results: Subjects with persistent DSA, 1:8 dilution DSA, and C1q DSA had higher incidence of CAV 2/3 compared the control group (17.6%, 13.3%, and 16.7% vs. 3.1%, respectively; P≤ .001). The incidence of CAV 2/3 between subjects with transient DSA and the control group was similar (2.8% vs. 3.1%; P = .888). Subjects with Class II DSA also had higher incidence of CAV 2/3 (7.6% vs. 3.1%; P = .039).

Conclusion: DSA that are persistent, 1:8 dilution positive, C1q positive, and Class II are associated with more severe grades of CAV. These DSA characteristics may prognosticate disease and warrant consideration for treatment.
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http://dx.doi.org/10.1111/ctr.14483DOI Listing
December 2021

Hypothermia promotes mitochondrial elongation In cardiac cells via inhibition of Drp1.

Cryobiology 2021 10 29;102:42-55. Epub 2021 Jul 29.

Cedars-Sinai Smidt Heart Institute, Barbra Streisand Women's Heart Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Hypothermia is a valuable clinical tool in mitigating against the consequences of ischemia in surgery, stroke, cardiac arrest and organ preservation. Protection is afforded principally by a reduction of metabolism, manifesting as reduced rates of oxygen uptake, preservation of ATP levels, and a curtailing of ischemic calcium overload. The effects of non-ischemic hypothermic stress are relatively unknown. We sought to investigate the effects of clinically mild-to-severe hypothermia on mitochondrial morphology, oxygen consumption and protein expression in normoxic hearts and cardiac cells. Normoxic perfusion of rat hearts at 28-32 °C was associated with inhibition of mitochondrial fission, evidenced by a reduced abundance of the active phosphorylated form of the fission receptor Drp1 (pDrp1). Abundance of the same residue was reduced in H9c2 cells subjected to hypothermic culture (25-32 °C), in addition to a reduced abundance of the Drp1 receptor MFF. Hypothermia-treated H9c2 cardiomyocytes exhibited elongated mitochondria and depressed rates of mitochondrial-associated oxygen consumption, which persisted upon rewarming. Hypothermia also promoted a reduction in mRNA expression of the capsaicin receptor TRPV1 in H9c2 cells. When normothermic H9c2 cells were transfected with TRPV1 siRNA we observed reduced pDrp1 and MFF abundance, elongated mitochondria, and reduced rates of mitochondrial-associated oxygen consumption, mimicking the effects of hypothermic culture. In conclusion hypothermia promoted elongation of cardiac mitochondria via reduced pDrp1 abundance which was also associated with suppression of cellular oxygen consumption. Silencing of TRPV1 in H9c2 cardiomyocytes reproduced the morphological and respirometric phenotype of hypothermia. This report demonstrates a novel mechanism of cold-induced inhibition of mitochondrial fission.
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http://dx.doi.org/10.1016/j.cryobiol.2021.07.013DOI Listing
October 2021

Recipient and surgical factors trigger severe primary graft dysfunction after heart transplant.

J Heart Lung Transplant 2021 09 10;40(9):970-980. Epub 2021 Jun 10.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). The International Society for Heart and Lung Transplantation (ISHLT) subdivides PGD into 3 grades of increasing severity. Most studies have assessed risk factors for PGD without distinguishing between PGD severity grade. We sought to identify recipient, donor and surgical risk factors specifically associated with mild/moderate or severe PGD.

Methods: We identified 734 heart transplant recipients at our institution transplanted between January 1, 2012 and December 31, 2018. PGD was defined according to modified ISHLT criteria. Recipient, donor and surgical variables were analyzed by multinomial logistic regression with mild/moderate or severe PGD as the response. Variables significant in single variable modeling were subject to multivariable analysis via penalized logistic regression.

Results: PGD occurred in 24% of the cohort (n = 178) of whom 6% (n = 44) had severe PGD. One-year survival was reduced in recipients with severe PGD but not in those with mild or moderate PGD. Multivariable analysis identified 3 recipient factors: prior cardiac surgery, recipient treatment with ACEI/ARB/ARNI plus MRA, recipient treatment with amiodarone plus beta-blocker, and 3 surgical factors: longer ischemic time, more red blood cell transfusions, and more platelet transfusions, that were associated with severe PGD. We developed a clinical risk score, ABCE, which provided acceptable discrimination and calibration for severe PGD.

Conclusions: Risk factors for mild/moderate PGD were largely distinct from those for severe PGD, suggesting a differing pathophysiology involving several biological pathways. Further research into mechanisms underlying the development of PGD is urgently needed.
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http://dx.doi.org/10.1016/j.healun.2021.06.002DOI Listing
September 2021

Intermediate-term outcomes of heart transplantation for cardiac amyloidosis in the current era.

Clin Transplant 2021 06 19;35(6):e14308. Epub 2021 Apr 19.

Smidt Cedars-Sinai Heart Institute, Los Angeles, CA, USA.

Background: Cardiac amyloidosis (CA) has been historically noted with poor outcomes after heart transplant (HTx). However, strict patient selection, appropriate multi-organ transplant, and aggressive post-transplant therapy can result in favorable outcomes. We present the experience in the largest single-center cohort of CA patients post-HTx in the recent era.

Methods: Between January 2010 and December 2018, 51 CA patients underwent HTx-13 light-chain amyloidosis (AL) and 38 transthyretin amyloidosis (ATTR), 49 were included. Endpoints included 3-year survival, freedom from cardiac allograft vasculopathy (CAV), and freedom from non-fatal major adverse cardiac events (NF-MACE).

Results: Overall 3-year survival was 81.6% (69.2% for AL and 86% for ATTR) and was comparable to survival for patients transplanted for non-amyloid restrictive cardiomyopathy (RCM) in the same period (89%, p = .46). Three-year freedom from CAV (84% vs. 89%, p = .98), NF-MACE (82% vs. 83%, p = .96), and any-treated rejection (95% vs. 89%, p = .54) were also comparable in both groups. No recurrence in amyloid was noted in endomyocardial biopsies. Six patients (46%) with AL amyloidosis underwent autologous stem cell transplant 1-year post-HTx, and two patients (8%) with variant ATTR-CA underwent combined heart-liver transplant due to cardiac cirrhosis.

Conclusion: In the current era, both AL and ATTR cardiac amyloidosis patients have acceptable outcomes after heart transplantation.
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http://dx.doi.org/10.1111/ctr.14308DOI Listing
June 2021

Total Artificial Heart as Bridge to Cardiac Retransplantation.

ASAIO J 2021 03;67(3):e77-e79

From the Department of Cardiology, Department of Cardiothoracic Surgery, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California.

Mechanical circulatory support has been performed as a bridge to cardiac retransplantation in selected patients with graft failure. However, there is limited published experience on the use and potential benefit of the total artificial heart (TAH) as a bridge to cardiac retransplantation. We report on our institutional experience with 3 patients that received TAH as a bridge to retransplant, with 1 patient surviving post-retransplantation. This case series demonstrates the high-risk nature of this undertaking in cardiac retransplant candidates and highlights the issue of sensitization portending greater risk for poor outcomes after TAH as bridge to retransplantation.
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http://dx.doi.org/10.1097/MAT.0000000000001217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326319PMC
March 2021

Consensus conference on heart-kidney transplantation.

Am J Transplant 2021 07 19;21(7):2459-2467. Epub 2021 Feb 19.

Stanford University, Palo Alto, California, USA.

Simultaneous heart-kidney transplant (sHK) has enabled the successful transplantation of patients with end-stage heart disease and concomitant kidney disease, with non-inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi-organ transplantation were also debated. The findings and consensus statements are presented.
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http://dx.doi.org/10.1111/ajt.16512DOI Listing
July 2021

Heart Transplantation for Giant Cell Myocarditis: A Case Series.

Transplant Proc 2021 Jan-Feb;53(1):348-352. Epub 2020 Dec 29.

Advanced Heart Disease and Heart Transplant Programs, Cedars-Sinai Smidt Heart Institute, Los Angeles, California.

Background: Giant cell myocarditis (GCM) has a poor prognosis without heart transplant, but post-transplant survival is unknown.

Purpose: To describe the post-transplant survival of patients with GCM at a large transplant center.

Methods: Seven patients underwent heart transplant for histologically confirmed GCM of the explanted heart. The median age was 59 years, and 43% (3 of 7) were female. All patients had cardiogenic shock, multiorgan failure, elevated troponin, and recurrent ventricular tachycardia, and some required mechanical circulatory support. All patients received rabbit antithymocyte globulin (rATG) in the perioperative period at a dose of 1.5 mg/kg daily for 1 to 5 days and 4 received intravenous immunoglobulin 1 g/kg daily for 2 days after rATG. All patients had early initiation of tacrolimus by first to third postoperative day depending on renal function, early mycophenolate, and high dose steroid. All were maintained using tacrolimus, mycophenolate, and prednisone.

Results: One patient had asymptomatic recurrence of GCM at 3 months, managed by up-titration of tacrolimus, and had asymptomatic 2R cellular rejection at 4 months, managed with steroid bolus. No patient had high-grade rejection. One patient died at 267 days, possibly of GCM. Six of 7 (86%) remain alive at a median of 842 days (2.3 years) post transplant.

Conclusions: Patients with GCM have excellent post-transplant survival with use of rATG and triple drug immunosuppressive therapy; however, some patients remain at risk for GCM recurrence after transplant, which may respond to augmented immunosuppression.
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http://dx.doi.org/10.1016/j.transproceed.2020.10.047DOI Listing
April 2021

Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients.

Am J Transplant 2021 07 11;21(7):2479-2488. Epub 2021 Feb 11.

Department of Cardiology, Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, California, USA.

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre-formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%-97%) and 6250 (5000-10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14-0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.
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http://dx.doi.org/10.1111/ajt.16420DOI Listing
July 2021

Association of vimentin antibody and other non-HLA antibodies with treated antibody mediated rejection in heart transplant recipients.

Hum Immunol 2020 Dec 9;81(12):671-674. Epub 2020 Oct 9.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.

Non-human leukocyte antigen (HLA) antibodies have been implicated in heart transplantation rejection. However, targets of non-HLA antibodies remain elusive. Here, we utilized a panel of multiplex beads-based assay to determine the specificity of non-HLA antibodies following heart transplantation. We utilized a selected cohort of recipients who did not have HLA donor specific antibodies, but were diagnosed with antibody mediated rejection and treated for antibody mediated rejection. We found the presence of vimentin antibody was associated with treated antibody mediated rejection. Our results suggest that, in heart transplant recipients who are suspected of AMR but in the absence of HLA donor specific antibodies, non-HLA antibodies should be examined.
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http://dx.doi.org/10.1016/j.humimm.2020.09.003DOI Listing
December 2020

cBIN1 Score (CS) Identifies Ambulatory HFrEF Patients and Predicts Cardiovascular Events.

Front Physiol 2020 25;11:503. Epub 2020 May 25.

Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, United States.

Background: Cardiac Bridging Integrator 1 (cBIN1) is a membrane deformation protein that generates calcium microdomains at cardiomyocyte t-tubules, whose transcription is reduced in heart failure, and is released into blood. cBIN1 score (CS), an inverse index of plasma cBIN1, measures cellular myocardial remodeling. In patients with heart failure with preserved ejection fraction (HFpEF), CS diagnoses ambulatory heart failure and prognosticates hospitalization. The performance of CS has not been tested in patients with heart failure with reduced ejection fraction (HFrEF).

Methods And Results: CS was determined from plasma of patients recruited in a prospective study. Two comparative cohorts consisted of 158 ambulatory HFrEF patients (left ventricular ejection fraction (LVEF) ≤ 40%, 57 ± 10 years, 80% men) and 115 age and sex matched volunteers with no known history of HF. N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were also analyzed for comparison. CS follows a normal distribution with a median of 0 in the controls, which increases to a median of 1.9 ( < 0.0001) in HFrEF patients. CS correlates with clinically assessed New York Heart Association Class ( = 0.007). During 1-year follow-up, a high CS (≥ 1.9) in patients predicts increased cardiovascular events (43% vs. 26%, = 0.01, hazard ratio 1.9). Compared to a model with demographics, clinical risk factors, and NT-proBNP, adding CS to the model improved the overall continuous net reclassification improvement (NRI 0.64; 95% CI 0.18-1.10; = 0.006). Although performance for diagnosis and prognosis was similar to CS, NT-proBNP did not prognosticate between patients whose NT-proBNP values were > 400 pg/ml.

Conclusion: CS, which is mechanistically distinct from NT-proBNP, successfully differentiates myocardial health between patients with HFrEF and matched controls. A high CS reflects advanced NYHA stage, pathologic cardiac muscle remodeling, and predicts 1-year risk of cardiovascular events in ambulatory HFrEF patients. CS is a marker of myocardial remodeling in HFrEF patients, independent of volume status.
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http://dx.doi.org/10.3389/fphys.2020.00503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326053PMC
May 2020

Acceptable Post-Heart Transplant Outcomes Support Temporary MCS Prioritization in the New OPTN|UNOS Heart Allocation Policy.

Transplant Proc 2021 Jan-Feb;53(1):353-357. Epub 2020 Jul 7.

Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States. Electronic address:

Background: Temporary mechanical circulatory support (MCS) devices are generally used short term to maintain adequate organ perfusion in patients with advanced heart failure and cardiogenic shock. Unacceptably high waitlist mortality in this cohort motivated changes to heart allocation policy, which recognized the severity of illness by prioritization for temporary MCS and broader sharing in the new U.S. donor heart allocation policy. We evaluated the post-heart transplant outcomes for patients bridged with temporary MCS, a control population not bridged with MCS, and a cohort bridged with durable MCS.

Methods: The heart transplant research database was queried to identify patients bridged with temporary MCS and bridged with durable MCS who went directly to heart transplant in our center. Temporary MCS included Impella, intra-aortic balloon pump, and extracorporeal membrane oxygenation. Post-transplant endpoints were assessed at 30 days, 6 months, and 1 year.

Results: From 2010 to 2017, a total of 23 patients were bridged to heart transplant with temporary MCS and 548 were transplanted without MCS bridge. Patients bridged with temporary MCS had younger age, lower body mass index, and higher frequencies of prior blood transfusion and Status 1 (1A/1B) listing at transplant compared to patients not bridged with MCS (all P < .001). Despite the severity of illness in patients bridged with temporary MCS, post-transplant outcomes were indistinguishable from those in patients transplanted without MCS bridge, with no difference in 30-day, 6-month, or 1-year survival or 1-year freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any-treated rejection, acute cellular rejection, or antibody-mediated rejection (P = .23-.97). Similarly, compared to 157 patients bridged with durable MCS, no differences in post-transplant outcomes were identified for the temporary MCS cohort (P = .15-.94).

Conclusion: Temporary MCS as a bridge to transplant achieves similar post-transplant outcomes at 1 year compared to no MCS and durable MCS. These encouraging findings support recent changes in the Organ Procurement and Transplantation Network | United Network Organ Sharing (OPTN|UNOS) adult heart allocation policy.
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http://dx.doi.org/10.1016/j.transproceed.2020.04.1819DOI Listing
May 2021

Heart transplantation in the era of the SARS-CoV-2 pandemic: Is it safe and feasible?

Clin Transplant 2020 10 24;34(10):e14029. Epub 2020 Jul 24.

Cedars-Sinai Smidt Heart Institute, Los Angeles, California, USA.

As the SARS-CoV-2-pandemic continues to unfold, the number of heart transplants completed in the United States has been declining steadily. The current case series examines the immediate short-term outcomes of seven heart transplant recipients transplanted during the SARS-CoV-2 pandemic. We hope to illustrate that with proper preparation, planning, and testing, heart transplantation can be continued during a pandemic. We assessed 7 patients transplanted from March 4, 2020, to April 15, 2020. The following endpoints were noted: in-hospital survival, in-hospital freedom from rejection, in-hospital nonfatal major cardiac adverse events (NF-MACE), severe primary graft dysfunction, hospital length of stay, and ICU length of stay. There were no expirations throughout the hospital admission. In addition, there were no patients with NF-MACE or treated rejection, and 1 patient developed severe primary graft dysfunction. Average length of stay was 17.2 days with a standard deviation of 5.9 days. ICU length of stay was 7.7 days with a standard deviation of 2.3 days. Despite the decreasing trend in completed heart transplants due to SARS-CoV-2, heart transplantation appears to be feasible in the immediate short term. Further follow-up is needed, however, to assess the impact of SARS-CoV-2 on post-heart transplant outcomes months after transplantation.
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http://dx.doi.org/10.1111/ctr.14029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361065PMC
October 2020

Successful Treatment of Severe COVID-19 Pneumonia With Clazakizumab in a Heart Transplant Recipient: A Case Report.

Transplant Proc 2020 Nov 7;52(9):2711-2714. Epub 2020 Jun 7.

Comprehensive Transplant Center, Transplant Immunotherapy Program, Cedars Sinai Medical Center, Los Angeles, California.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by an overwhelming cytokine response. Various treatment strategies have been attempted.

Methods And Results: A 61-year-old man with heart transplantation in 2017 presented with fever, cough, and dyspnea, and was confirmed positive for coronavirus disease 2019 (COVID-19). Laboratory tests showed significant elevations in C-reactive protein and interleukin-6 (IL-6). Echocardiogram showed left ventricular ejection fraction 58% (with ejection fraction 57% 6 months prior). Given the lack of clear management guidelines, the patient was initially managed symptomatically. However, the patient subsequently had a rapid respiratory deterioration with worsening inflammatory markers on day 5 of admission. Tocilizumab (anti-IL-6R) was in low supply in the hospital. The patient was offered clazakizumab (anti-IL-6) for compassionate use. Patient received 25 mg intravenously × 1 dose. Within 24 hours, he showed significant improvement in symptoms, oxygen requirements, radiological findings, and inflammatory markers. There was a transient leukopenia that improved in 4 days. He was discharged home on day 11, with negative nasopharyngeal SARS-CoV-2 PCR as an outpatient on day 35, development of positive serum COVID-19 IgG antibody, and he continued to do well on day 60, with no heart-related symptoms.

Conclusion: Clazakizumab is a monoclonal antibody against human IL-6, which may be helpful in inhibiting the cytokine response to SARS-CoV-2 in COVID-19. Although not yet FDA approved, it is being investigated for treatment of renal antibody-mediated rejection. Clinical trials of clazakizumab for treatment of COVID-19 are underway worldwide.
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http://dx.doi.org/10.1016/j.transproceed.2020.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275980PMC
November 2020

Donor organ evaluation in the era of coronavirus disease 2019: A case of nosocomial infection.

J Heart Lung Transplant 2020 06 12;39(6):611-612. Epub 2020 Apr 12.

Smidt Cedars-Sinai Heart Institute, Los Angeles, California. Electronic address:

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http://dx.doi.org/10.1016/j.healun.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152866PMC
June 2020

Platelet Mapping by Thromboelastography and Whole Blood Aggregometry in Adult Patients Supported by Mechanical Circulatory Support Device on Aspirin Therapy.

J Extra Corpor Technol 2020 Mar;52(1):13-21

Cedars Sinai Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, California.

Patients on mechanical circulatory support (MCS) devices are placed on aspirin and may require platelet function testing (PFT) to monitor the adequacy of therapy. Routine laboratory PFT is performed using whole blood aggregation (WBA) which typically has a long turnaround time (4-5 hours) and may not be readily available. By contrast, platelet mapping by thromboelastography (TPM) can provide results within 45 minutes. The objective of this study was to compare the results of TPM with WBA. We compared platelet mapping maximal amplitude (MA) by TPM with that of arachidonic acid (AA) to WBA with AA by impedance. We analyzed paired samples where both TPM and WBA were available. Of 45 paired samples, 34 were from 29 MCS patients and 11 were from non-MCS patients. When applying institutional interpretation guidelines with an MA cutoff of ≤40 mm, WBA vs TPM MA in non-MCS and MCS patients correlated well with an accuracy of 100 and 94.4%, respectively. MA >40 had poor correlation with an accuracy of 37.5%. Irrespective of MA value, TPM AA inhibition expressed in percent of inhibition had poor accuracy. When used with proper guidelines for interpretation, specifically when MA ≤ 40 mm, TPM is a suitable and reliable test to use for MCS patients on aspirin.
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http://dx.doi.org/10.1182/ject-1900029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138126PMC
March 2020

Mechanical circulatory support for cardiac amyloidosis.

Clin Transplant 2019 10 29;33(10):e13663. Epub 2019 Jul 29.

Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, California.

Background: Cardiac amyloidosis, typically from abnormal deposition of AL or ATTR amyloid protein, can result in heart failure requiring transplantation (HTx). The role of mechanical circulatory support (MCS) is not well-established. The purpose of this study was to present our experience with MCS in patients with cardiac amyloidosis.

Methods: Consecutive patients with cardiac amyloidosis who received MCS at Cedars-Sinai Medical Center between 2010 and 2018 were reviewed. Clinical characteristics and outcomes were compared to a control group of MCS patients without amyloid matched 2:1 for age and INTERMACS Profile.

Results: 11 amyloid patients underwent durable MCS, two with paracorporeal biventricular assist devices and 9 with total artificial hearts. No patients received isolated left ventricular assist device support. By 1 year, 9 (82%) of patients in the MCS-Amyloid group had been transplanted and 2 (18%) had died. In the MCS-No Amyloid group, by 1 year, 8 (36%) of patients had been transplanted, 10 (46%) had died, and 4 (18%) were still living with MCS.

Conclusions: Over a 9-year period, patients with amyloid cardiomyopathy who required MCS at our institution all received durable biventricular MCS. For carefully selected patients, this approach is feasible with acceptable outcomes as bridge to transplantation.
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http://dx.doi.org/10.1111/ctr.13663DOI Listing
October 2019

Combined heart and kidney transplantation-Is there a protective effect against cardiac allograft vasculopathy using intravascular ultrasound?

J Heart Lung Transplant 2019 09 19;38(9):956-962. Epub 2019 Jun 19.

Cardiology, Cedars-Sinai Smidt Heart Institute, Los Angeles, California. Electronic address:

Background: Because cardiac and renal disease are physiologically related and often coexist, the prevalence of combined heart and kidney transplantation (HKTx) has significantly increased over the last few years. It has been suggested that combined organ allografts modulate the immune system favorably for one or both allografts resulting in successful clinical outcomes. However, whether the addition of kidney transplantation has a protective immune effect against developing cardiac allograft vasculopathy (CAV) has not been fully investigated.

Methods: From March 2010 to September 2018, 30 HKTx recipients who had baseline (4-6 weeks) and 1-year intravascular ultrasound (IVUS) were matched with 60 isolated heart transplant (HTx-alone) recipients using propensity scores. First-year changes in maximal intimal thickness (MIT), maximal intimal area (MIA), maximal percent stenosis (MPS), percent atheroma volume (PAV), and incidence of rapid plaque progression were compared between the groups.

Results: First-year coronary plaque progression was significantly decreased in HKTx recipients compared with HTx-alone recipients by change in the MIT (0.11 ± 0.14 mm vs 0.40 ± 0.32 mm, p < 0.001), MIA (0.52 ± 1.52 mm vs 1.86 ± 2.68 mm, p = 0.002), MPS (2.10% ± 5.64 percentage points vs 7.22% ± 8.59 percentage points, p = 0.001), and PAV (1.62% ± 3.07 percentage points vs 5.90% ± 5.92 percentage points, p < 0.001). Rapid plaque progression occurred in 2 of 30 in HKTx (6.7%) and in 22 of 60 HTx alone (36.7%), p = 0.002.

Conclusions: Combined heart and kidney transplantation is associated with a decrease in CAV by coronary plaque progression on IVUS. These results suggest that HKTx may have an immune modulating benefit over HTx alone.
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http://dx.doi.org/10.1016/j.healun.2019.06.012DOI Listing
September 2019

Myocardial hypothermia increases autophagic flux, mitochondrial mass and myocardial function after ischemia-reperfusion injury.

Sci Rep 2019 07 10;9(1):10001. Epub 2019 Jul 10.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Animal studies have demonstrated beneficial effects of therapeutic hypothermia on myocardial function, yet exact mechanisms remain unclear. Impaired autophagy leads to heart failure and mitophagy is important for mitigating ischemia/reperfusion injury. This study aims to investigate whether the beneficial effects of therapeutic hypothermia are due to preserved autophagy and mitophagy. Under general anesthesia, the left anterior descending coronary artery of 19 female farm pigs was occluded for 90 minutes with consecutive reperfusion. 30 minutes after reperfusion, we performed pericardial irrigation with warm or cold saline for 60 minutes. Myocardial tissue analysis was performed one and four weeks after infarction. Therapeutic hypothermia induced a significant increase in autophagic flux, mitophagy, mitochondrial mass and function in the myocardium after infarction. Cell stress, apoptosis, inflammation as well as fibrosis were reduced, with significant preservation of systolic and diastolic function four weeks post infarction. We found similar biochemical changes in human samples undergoing open chest surgery under hypothermic conditions when compared to the warm. These results suggest that autophagic flux and mitophagy are important mechanisms implicated in cardiomyocyte recovery after myocardial infarction under hypothermic conditions. New therapeutic strategies targeting these pathways directly could lead to improvements in prevention of heart failure.
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http://dx.doi.org/10.1038/s41598-019-46452-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620356PMC
July 2019

Does ex vivo perfusion lead to more or less intimal thickening in the first-year post-heart transplantation?

Clin Transplant 2019 08 11;33(8):e13648. Epub 2019 Jul 11.

Department of Cardiology, Cedars-Sinai Smidt Heart Institute, Los Angeles, California.

Background: The Organ Care System (OCS), an ex vivo heart perfusion platform, represents an alternative to the current standard of cold organ storage that sustains the donor heart in a near-physiologic state. Previous reports showed that this system had significantly shortened the cold ischemic time from standard cold storage (CS). However, the effect of reduced ischemic injury against the coronary vascular bed has not been examined by intravascular ultrasound (IVUS).

Methods: Between August 2011 and February 2013, heart transplant (HTx) candidates enrolled in the PROCEED 2 trial were randomized to either CS or OCS. IVUS was performed at 4-6 weeks (baseline) and repeated 1 year after transplantation. The change in maximal intimal thickness (MIT) and other clinical outcomes were examined.

Results: Thirty-nine patients were randomized and underwent HTx by OCS (n=16) or CS (n=18). Of these, 18 patients (OCS: n=5, CS: n=13) with paired IVUS were examined. There were no significant differences in the change of MIT and other clinical outcomes between the groups.

Conclusion: The incidence of cardiac allograft vasculopathy in donor hearts preserved with the OCS versus CS was similar. These results suggest that this ex vivo allograft perfusion system is a promising and valid platform for donor heart transportation.
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http://dx.doi.org/10.1111/ctr.13648DOI Listing
August 2019

Controversies in the Postoperative Management of the Critically Ill Heart Transplant Patient.

Anesth Analg 2019 10;129(4):1023-1033

From the Departments of Anesthesiology.

Heart transplant recipients are susceptible to a number of complications in the immediate postoperative period. Despite advances in surgical techniques, mechanical circulatory support (MCS), and immunosuppression, evidence supporting optimal management strategies of the critically ill transplant patient is lacking on many fronts. This review identifies some of these controversies with the aim of stimulating further discussion and development into these gray areas.
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http://dx.doi.org/10.1213/ANE.0000000000004220DOI Listing
October 2019

Combined Heart and Kidney Transplantation: Clinical Experience in 100 Consecutive Patients.

J Am Heart Assoc 2019 02;8(4):e010570

1 Division of Cardiology Cedars-Sinai Smidt Heart Institute the Multiorgan Transplant Program Cedars-Sinai Medical Center Los Angeles CA.

Background Combined heart and kidney transplantation ( HKT x) is performed in patients with severe heart failure and advanced renal insufficiency. We analyzed the long-term survival after HKT x, the influence of age and dialysis status, the rates of cardiac rejection, and the influence of sensitization. Methods and Results From June 1992 to December 2016, we performed 100 HKT x procedures. We compared older (≥60 years, n=53) with younger (<60 years, n=47) recipients, and recipients on preoperative dialysis (n=49) and not on dialysis (n=51). We analyzed actuarial freedom from any cardiac rejection, acute cellular rejection, and antibody-mediated rejection, and survival rates by sensitized status with panel-reactive antibody levels <10%, 10% to 50%, and >50%, and compared these survival rates with those from the United Network for Organ Sharing database. There was no difference in 15-year survival between the 2 age groups (35±12.4% and 49±17.3%, ≥60 versus <60 years; P=0.45). There was no difference in 15-year survival between the dialysis and nondialysis groups (44±13.4% and 37±15.2%, P=0.95). Actuarial freedom from any cardiac rejection ( acute cellular rejection >0 or antibody-mediated rejection >0) was 92±2.8% and 84±3.8%, acute cellular rejection (≥2R/3A) 98±1.5% and 94±2.5%, and antibody-mediated rejection (≥1) 96±2.1% and 93±2.6% at 30 days and 1 year after HKT x. There was no difference in the 5-year survival among recipients by sensitization status with panel-reactive antibody levels <10%, 10% to 50%, and >50% (82±5.9%, 83±10.8%, and 92±8.0%; P=0.55). There was no difference in 15-year survival after HKT x between the United Network for Organ Sharing database and our center (38±3.2% and 40±10.1%, respectively; P=0.45). Conclusions HKT x is safe to perform in patients 60 years and older or younger than 60 years and with or without dialysis dependence, with excellent outcomes. The degree of panel-reactive antibody sensitization did not appear to affect survival after HKT x.
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http://dx.doi.org/10.1161/JAHA.118.010570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405671PMC
February 2019

Predicted heart mass is the optimal metric for size match in heart transplantation.

J Heart Lung Transplant 2019 02 27;38(2):156-165. Epub 2018 Sep 27.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Donor-recipient size match is traditionally assessed by body weight. We assessed the ability of 5 size match metrics-predicted heart mass (PHM), weight, height, body mass index (BMI) and body surface area (BSA)-to predict 1-year mortality after heart transplant and to assess the effect of size match on donor heart turn down for size.

Methods: The study cohort comprised 19,168 adult heart transplant recipients in the United Network for Organ Sharing registry between 2007 and 2016. Each size match metric was divided into 7 equally sized groups using the donor-recipient ratio for each metric. Single and multivariable Cox proportional hazard models for mortality 1 year after transplant were constructed.

Results: Recipients in the severely (donor-recipient PHM ratio 0.54-0.86) undersized group for PHM experienced increased mortality, with a hazard ratio of 1.34 (95% confidence interval, 1.13-1.59; p < 0.001). There was no increased risk of death at 1 year if donors were undersized for weight, height, BMI, or BSA. We found that 32% of heart offers turned down for donor size would be acceptable using a PHM threshold of 0.86 or greater and that 14% of offers accepted (most of which are female donor to male recipient) were below this threshold.

Conclusions: PHM is the optimal donor-recipient size match metric for prediction of mortality after heart transplant. Many offers turned down for donor size were above the threshold for adequacy of size match by PHM identified, and thus, the use of PHM could improve donor heart utilization and post-transplant survival.
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http://dx.doi.org/10.1016/j.healun.2018.09.017DOI Listing
February 2019

Association of a Novel Diagnostic Biomarker, the Plasma Cardiac Bridging Integrator 1 Score, With Heart Failure With Preserved Ejection Fraction and Cardiovascular Hospitalization.

JAMA Cardiol 2018 12;3(12):1206-1210

Division of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Importance: Transverse tubule remodeling is a hallmark of heart failure. Cardiac bridging integrator 1 (cBIN1) is a circulating membrane scaffolding protein that is essential for transverse tubule health, and its plasma level declines with disease.

Objective: To determine if a cBIN1-derived score can serve as a diagnostic biomarker of heart failure with preserved ejection fraction (HFpEF).

Design, Setting, And Participants: In this cohort study, the cBIN1 score (CS) was determined from enzyme-linked immunoabsorbent assay-measured plasma cBIN1 concentrations from study participants in an ambulatory heart failure clinic at Cedars-Sinai Medical Center. Consecutive patients with a confirmed diagnosis of heart failure with preserved ejection fraction (HFpEF; defined by a left ventricular ejection fraction ≥50%) were recruited from July 2014 to November 2015 and compared with age-matched and sex-matched healthy volunteers with no known cardiovascular diagnoses and participants with risk factors for heart failure but no known HFpEF. Baseline characteristics and 1-year longitudinal clinical information were obtained through electronic medical records. Data analysis occurred from November 2016 to November 2017.

Main Outcomes And Measures: The analysis examined the ability of the CS and N-terminal pro-B-type natriuretic peptide (NT-proBNP) results to differentiate among patients with HFpEF, healthy control participants, and control participants with risk factors for heart failure. We further explored the association of the CS with future cardiovascular hospitalizations.

Results: A total of 52 consecutive patients with a confirmed diagnosis of HFpEF were enrolled (mean [SD] age, 57 [15] years; 33 [63%] male). The CS values are significantly higher in the patients with HFpEF (median [interquartile range (IQR)], 1.85 [1.51-2.28]) than in the 2 control cohorts (healthy control participants: median [IQR], -0.03 [-0.48 to 0.41]; control participants with risk factors only: median [IQR], -0.08 [-0.75 to 0.42]; P < .001). For patients with HFpEF, the CS outperforms NT-proBNP when the comparator group was either healthy control participants (CS: area under curve [AUC], 0.98 [95% CI, 0.96-1.00]; NT-proBNP level: AUC, 0.93 [95% CI, 0.88-0.99]; P < .001) or those with risk factors (CS: AUC, 0.98 [95% CI, 0.97-1.00]; NT-proBNP: AUC, 0.93 [95% CI, 0.88-0.99]; P < .001). Kaplan-Meier analysis of 1-year cardiovascular hospitalizations adjusted for age, sex, body mass index, and NT-proBNP levels reveals that patients with HFpEF with CS greater than or equal to 1.80 have a hazard ratio of 3.8 (95% CI, 1.3-11.2; P = .02) for hospitalizations compared with those with scores less than 1.80.

Conclusions And Relevance: If further validated, the plasma CS, a marker of transverse tubule dysfunction, may serve as a biomarker of cardiomyocyte remodeling that has the potential to aide in the diagnosis of HFpEF.
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http://dx.doi.org/10.1001/jamacardio.2018.3539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583707PMC
December 2018

Dual-organ transplantation in older recipients: outcomes after heart-kidney transplant versus isolated heart transplant in patients aged ≥65 years.

Interact Cardiovasc Thorac Surg 2019 01;28(1):45-51

Cedars-Sinai Heart Institute, Los Angeles, CA, USA.

Objectives: Combined heart-kidney transplantation has successful outcomes. With an increasing number of patients with end-stage heart disease, there is a high incidence of significant renal insufficiency that may necessitate combined heart-kidney transplant. Outcomes for heart-kidney transplant recipients aged ≥65 years are not well described.

Methods: Between 2010 and 2015, 163 recipients ≥65 years of age were transplanted in a single centre: 12 heart-kidney and 151 isolated heart transplants. Outcomes assessed were estimated glomerular filtration rate at 1, 6 and 12 months after transplant, the need for dialysis, 1-year survival, 1-year freedom from rejection, 1-year freedom from cardiac allograft vasculopathy and 1-year freedom from non-fatal major adverse cardiac events.

Results: Recipient ages were 67.8 ± 1.6 and 69.0 ± 2.8 years for heart-kidney transplant and isolated heart transplant, and pretransplant estimated glomerular filtration rates were 26.6 ± 9.4 vs 55.2 ± 18.9, respectively. At 1 month (66.3 ± 31.4 vs 67.2 ± 28.0, P = 0.92), 6 months (68.1 ± 21.3 vs 60.5 ± 19.6, P = 0.20) and 12 months (58.6 ± 21.5 vs 52.4 ± 18.5, P = 0.27) post-transplant, estimated glomerular filtration rate was similar for heart-kidney transplant versus isolated heart transplant. There was a trend towards reduced 1-year freedom from temporary dialysis after heart-kidney transplant relative to isolated heart transplant (75.0% vs 90.4%, P = 0.06) without a difference in 1-year freedom from chronic dialysis (100% vs 95.2%, P = 0.46). There were no differences in 1-year survival, 1-year freedom from any treated rejection, acute cellular rejection, antibody-mediated rejection, cardiac allograft vasculopathy and non-fatal major adverse cardiac events.

Conclusions: For patients ≥65 years old, heart-kidney transplant can achieve outcomes on par with heart transplant alone.
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http://dx.doi.org/10.1093/icvts/ivy202DOI Listing
January 2019

High Molecular Weight von Willebrand Factor Multimer Loss and Bleeding in Patients with Short-Term Mechanical Circulatory Support Devices: A Case Series.

J Extra Corpor Technol 2018 06;50(2):77-82

Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

Acquired von Willebrand syndrome (VWS) due to loss of high-molecular-weight multimers (HMWMs) has been reported with longer term mechanical devices and is associated with mucosal bleeding, a primary hemostasis type of bleeding. However, little is known whether a similar defect occurs in patients with short-term mechanical circulatory support (STMCS) devices. We reviewed von Willebrand factor (VWF) profiles in patients with STMCS devices who underwent VWS workup from December 2015 to March 2017 at an academic quaternary care hospital. There were a total of 18 patients (57.0 ± 12.7 years old; 83.3% male) including nine with mucosal bleeding and nine with decreasing hemoglobin. The STMCS devices included Impella (n = 11), Impella and right ventricular assist device (n = 2), and an extracorporeal membrane oxygenator (n = 5). The mean HMWM by quantitative VWF multimer analysis was 3.6% ± 1.3% (normal cutoff: 18-34%). In all 10 cases in which VWF activity, fibrinogen, factor VIII, or VWF antigen level were obtained, they were either normal or elevated. All cases demonstrated high normal or elevated levels of low molecular weight multimers (LMWMs). These findings are consistent with type 2 VWS (qualitative defect). This is the first study that quantitatively describes STMCS device-associated HMWM loss, which may contribute to mucosal bleeding. This finding may have implications for intraoperative management during implantation of longer term devices or heart transplantation or other surgery while on STMCS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002638PMC
June 2018

Use of durable mechanical circulatory support on outcomes of heart-kidney transplantation.

Interact Cardiovasc Thorac Surg 2018 11;27(5):773-777

Cedars-Sinai Heart Institute, Los Angeles, CA, USA.

Objectives: Previous studies have demonstrated that preheart transplant mechanical circulatory support (MCS) can lead to a small but significant increase in mortality. However, data on outcomes of patients with MCS who require simultaneous heart-kidney transplant are limited.

Methods: A retrospective review of simultaneous heart-kidney transplantations (HKTxs) performed at a single institution over a 5-year period was performed. Patients were divided based on the preoperative use of durable MCS. Renal graft-related end points were evaluated, including glomerular filtration rate following transplantation, prevalence of delayed renal graft function and freedom from antibody and cellular-mediated graft rejection. Patient-specific outcomes, including survival and frequency of non-fatal major adverse cardiac events at 1 year, were additionally assessed.

Results: During the study period, 50 HKTxs were performed, 14 of which had preoperative MCS. HKTx patients with and without MCS implantations had a similar prevalence of delayed graft function (57.1% vs 50.0%; P = 0.757). A numerical trend was observed towards a reduced glomerular filtration rate 1-month post-transplant in patients without an MCS device (81.2 ± 32.8 vs 64.4 ± 27.5; P = 0.072), but no significant difference was observed at 6 and 12 months. No significant difference was observed on the need for post-transplant renal replacement therapy, non-fatal major adverse cardiac events, freedom from graft rejection and overall survival at 1 year.

Conclusions: The use of preoperative MCS in patients undergoing combined HKTx was not found to affect renal graft function post-transplantation and does not seem to be associated with increase in morbidity or mortality.
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http://dx.doi.org/10.1093/icvts/ivy156DOI Listing
November 2018

Interagency registry for mechanically assisted circulatory support report on the total artificial heart.

J Heart Lung Transplant 2018 11 26;37(11):1304-1312. Epub 2018 Apr 26.

Kirklin Institute for Research in Surgical Outcomes, University of Alabama at Birmingham, Birmingham, Alabama.

Background: We sought to better understand the patient population who receive a temporary total artificial heart (TAH) as bridge to transplant or as bridge to decision by evaluating data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database.

Methods: We examined data related to survival, adverse events, and competing outcomes from patients who received TAHs between June 2006 and April 2017 and used hazard function analysis to explore risk factors for mortality.

Results: Data from 450 patients (87% men; mean age, 50 years) were available in the INTERMACS database. The 2 most common diagnoses were dilated cardiomyopathy (50%) and ischemic cardiomyopathy (20%). Risk factors for right heart failure were present in 82% of patients. Most patients were INTERMACS Profile 1 (43%) or 2 (37%) at implantation. There were 266 patients who eventually underwent transplantation, and 162 died. Overall 3-, 6-, and 12-month actuarial survival rates were 73%, 62%, and 53%, respectively. Risk factors for death included older age (p = 0.001), need for pre-implantation dialysis (p = 0.006), higher creatinine (p = 0.008) and lower albumin (p < 0.001) levels, and implantation at a low-volume center (≤10 TAHs; p < 0.001). Competing-outcomes analysis showed 71% of patients in high-volume centers were alive on the device or had undergone transplantation at 12 months after TAH implantation vs 57% in low-volume centers (p = 0.003).

Conclusions: Patients receiving TAHs have rapidly declining cardiac function and require prompt intervention. Experienced centers have better outcomes, likely related to patient selection, timing of implantation, patient care, and device management. Organized transfer of knowledge to low-volume centers could improve outcomes.
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http://dx.doi.org/10.1016/j.healun.2018.04.004DOI Listing
November 2018

Combining Stem Cell Therapy for Advanced Heart Failure and Ventricular Assist Devices: A Review.

ASAIO J 2018 Sep/Oct;64(5):e80-e87

Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

The use of stem cell therapy in combination with a left ventricular assist device (LVAD) for patients with advanced heart failure (HF) is an attractive concept with the potential to alter the natural history of HF. Cell therapy trials for HF have demonstrated excellent safety and encouraging results, but current rates of myocardial recovery after LVAD implantation are limited. Early trials combining these 2 therapies to increase the likelihood of recovery and to potentially obviate the need for subsequent transplantation appear promising. Additionally, the application of cell therapy to patients undergoing LVAD implantation as a bridge to cardiac transplantation creates an opportunity to examine cardiac tissue before and after treatment and to study the mechanism of benefit. Despite the promise, there is a paucity of data for the combination of stem cell therapy with LVAD insertion in patients with HF. Of 11 case series or clinical trials, the largest enrolled 30 patients. We highlight clinical trials using stem cell therapy for end-stage HF most relevant to an LVAD patient population and comprehensively review the preclinical and clinical studies of combined stem cell therapy and long-term mechanical circulatory support. Based on the available clinical trials, the combination of stem cell therapy and LVAD support is a promising approach but requires further clinical refinement, with additional clinical data and larger numbers of patients required to support its clinical application.
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http://dx.doi.org/10.1097/MAT.0000000000000782DOI Listing
March 2019
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