Publications by authors named "Susan Restaino"

65 Publications

Impact of Temporary Percutaneous Mechanical Circulatory Support Before Transplantation in the 2018 Heart Allocation System.

JACC Heart Fail 2022 Jan 10;10(1):12-23. Epub 2021 Nov 10.

Milstein Division of Cardiology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA. Electronic address:

Objectives: This analysis sought to investigate the waitlist and post-transplant outcomes of individuals bridged to transplantation by using temporary percutaneous endovascular mechanical circulatory support (tMCS) through a status 2 designation (cardiogenic shock and exception).

Background: The 2018 donor heart allocation policy change granted a status 2 designation to patients supported with tMCS.

Methods: Adult patients in the United Network for Organ Sharing registry after October 18, 2018 who received a status 2 designation for tMCS were included and grouped by their status 2 criteria: cardiogenic shock with hemodynamic criteria (CS-HD), cardiogenic shock without hemodynamic criteria before tMCS (CS-woHD), and exception. Baseline characteristics, waitlist events (death and delisting), and post-transplant outcomes were compared.

Results: A total of 2,279 patients met inclusion criteria: 68.6% (n = 1,564) with CS-HD, 3.2% (n = 73) with CS-woHD, and 28.2% (n = 642) with exceptions. A total of 64.2% of patients underwent heart transplantation within 14 days of status 2 listing or upgrade, and 1.9% died or were delisted for worsening clinical condition. Among the 35.8% who did not undergo transplantation following 14 days, only 2.8% went on to receive a left ventricular assist device (LVAD). The 30-day transplantation likelihood was similar among groups: 80.1% for the CS-HD group vs 79.7% for the exception group vs 73.3% for the CS-woHD group; P = 0.31. However, patients who met criteria for CS-woHD had 2.3-fold greater risk of death or delisting (95% CI: 1.10-4.75; P = 0.03) compared with CS-HD patients after multivariable adjustment. Pre-tMCS hemodynamics were not associated with adverse waitlist events.

Conclusions: The use of tMCS is an efficient, safe, and effective strategy as a bridge to transplantation; however, patients with CS-woHD may represent a high-risk cohort. Transition to a durable LVAD was a rare event in this group.
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http://dx.doi.org/10.1016/j.jchf.2021.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724562PMC
January 2022

Chronic intermittent intravenous immunoglobulin in heart transplant recipients with elevated donor-specific antibody levels.

Clin Transplant 2021 Oct 27:e14524. Epub 2021 Oct 27.

Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA.

Donor-specific antibodies (DSA) are associated with antibody-mediated rejection (AMR) and poor patient survival. In heart transplant, the efficacy of intermittent intravenous immunoglobulin (IVIg) in reducing de novo DSA levels and treating AMR has not been characterized. We retrospectively studied a cohort of 19 patients receiving intermittent IVIg for elevated DSA and examined changes in DSA levels and graft function. Intermittent IVIg infusions were generally safe and well tolerated. Overall, 23 of 62 total DSA (37%) were undetectable after treatment, 21 DSA (34%) had MFI decrease by more than 25%, and 18 (29%) had MFI decrease by less than 25% or increase. The average change in MFI was -51% ± 71% (P < .001). Despite reductions in DSA, among the six patients (32%) with biopsy-confirmed AMR, left ventricular ejection fraction (LVEF) decreased in five (83%) and cardiac index (CI) decreased in three (50%). Conversely, LVEF increased in 91% and CI increased in 70% of biopsy-negative patients. All six AMR patients were readmitted during treatment, four for confirmed or suspected rejection. IVIg infusions may stabilize the allograft in patients with elevated DSA and negative biopsies, but once AMR has developed does not appear to improve allograft function despite decreasing DSA levels.
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http://dx.doi.org/10.1111/ctr.14524DOI Listing
October 2021

Transcriptomic heterogeneity of antibody mediated rejection after heart transplant with or without donor specific antibodies.

J Heart Lung Transplant 2021 11 8;40(11):1472-1480. Epub 2021 Jul 8.

Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York. Electronic address:

Background: Antibody mediated rejection (AMR) is an increasingly studied cause of graft failure after heart transplantation. AMR diagnosis previously required the detection of circulating donor specific antibodies (DSA); however, the most recent criteria only require pathological findings. This classification defined a subset of patients with AMR, yet without known antibodies. Here, we sought to evaluate differences in the transcriptome profile associated with different types of AMR.

Methods: RNA sequencing was used on endomyocardial biopsies to analyze and compare transcriptomic profiles associated with different subtypes of AMR defined by immunopathological and histopathological findings, as well as the presence or absence of DSA. Gene expression profiles were characterized for each diagnostic group.

Results: The most divergent gene expression profiles were observed between patients with or without DSA. AMR subtypes associated with DSA showed expression of signature genes involved in monocyte activation and response to interferon. There was also substantial difference between the transcriptomic profiles of AMR defined by histopathological and immunopathological findings, the latter being associated with expression of mucin genes. In contrast, there was no differential RNA expression between patients with pAMR1i without DSA and those without AMR. Likewise, no differential expression was observed between patients with pAMR1h with DSA and pAMR2.

Conclusions: Overall, our studies reveal different expression profiles in endomyocardial biopsies in relation to some key criteria used to diagnose AMR. These findings support the view that the diagnosis of AMR encompasses several phenotypes that may rely on distinct mechanisms of injury.
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http://dx.doi.org/10.1016/j.healun.2021.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571048PMC
November 2021

A Rare Case of Disseminated Tuberculosis and Hematological Malignancy in a Heart Transplant Recipient.

Transplant Proc 2021 Oct 13;53(8):2626-2629. Epub 2021 Aug 13.

Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA. Electronic address:

A 77-year-old man who underwent a heart transplant 7 years ago presented with multiple bloody bowel movements. Endoscopic and histologic evaluation revealed chronic active ileitis, granulomatous inflammation, multinucleated giant cells, and a rare, equivocal acid-fast bacterium in the terminal ileum. Positive sputum cultures for Mycobacterium tuberculosis and acid-fast bacilli established a diagnosis of intestinal tuberculosis, and RIPE (rifabutin, isoniazid, pyrazinamide, ethambutol) therapy was initiated. Elevated IgG levels on quantitative immunoglobulin testing and a bone marrow biopsy specimen of ≥60% plasma cells confirmed the diagnosis of multiple myeloma that later transformed into its aggressive form, plasma cell leukemia. Induction chemotherapy was initiated; however, the patient experienced retroperitoneal bleeding and pancytopenias, limiting the continuation of chemotherapy, and as a result, the patient was transitioned to palliative care.
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http://dx.doi.org/10.1016/j.transproceed.2021.07.037DOI Listing
October 2021

How can we better inform our patients about post-heart transplantation survival? A conditional survival analysis.

Clin Transplant 2021 Nov 12;35(11):e14449. Epub 2021 Sep 12.

Department of Medicine, Milstein Division of Cardiology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.

Background: Conditional survival (CS) is a dynamic method of survival analysis that provides an estimate of how an individual's future survival probability changes based on time post-transplant, individual characteristics, and post-transplant events. This study sought to provide post-transplant CS probabilities for heart transplant recipients based on different prognostic variables and provide a discussion tool for the providers and the patients.

Methods: Adult heart transplant recipients from January 1, 2004, through October 18, 2018, were identified in the UNOS registry. CS probabilities were calculated using data from Kaplan-Meier survival estimates.

Results: CS probability exceeded actuarial survival probability at all times post-transplant. Women had similar short-term, but greater long-term CS than men at all times post-transplant (10-year CS 1.8-11.5% greater [95% CI 1.2-12.9]). Patients with ECMO or a surgical BiVAD had decreased survival at the time of transplant, but their CS was indistinguishable from all others by 1-year post-transplant. Rejection and infection requiring hospitalization during the first year were associated with a persistently decreased CS probability.

Conclusions: In this study, we report differential conditional survival outcomes based on time, patient characteristics, and clinical events post-transplant, providing a dynamic assessment of survival. The survival probabilities will better inform patients and clinicians of future outcomes.
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http://dx.doi.org/10.1111/ctr.14449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8697356PMC
November 2021

Plasma kallikrein predicts primary graft dysfunction after heart transplant.

J Heart Lung Transplant 2021 10 10;40(10):1199-1211. Epub 2021 Jul 10.

Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York. Electronic address:

Background: Primary graft dysfunction (PGD) is the leading cause of early mortality after heart transplant. Pre-transplant predictors of PGD remain elusive and its etiology remains unclear.

Methods: Microvesicles were isolated from 88 pre-transplant serum samples and underwent proteomic evaluation using TMT mass spectrometry. Monte Carlo cross validation (MCCV) was used to predict the occurrence of severe PGD after transplant using recipient pre-transplant clinical characteristics and serum microvesicle proteomic data. Putative biological functions and pathways were assessed using gene set enrichment analysis (GSEA) within the MCCV prediction methodology.

Results: Using our MCCV prediction methodology, decreased levels of plasma kallikrein (KLKB1), a critical regulator of the kinin-kallikrein system, was the most predictive factor identified for PGD (AUROC 0.6444 [0.6293, 0.6655]; odds 0.1959 [0.0592, 0.3663]. Furthermore, a predictive panel combining KLKB1 with inotrope therapy achieved peak performance (AUROC 0.7181 [0.7020, 0.7372]) across and within (AUROCs of 0.66-0.78) each cohort. A classifier utilizing KLKB1 and inotrope therapy outperforms existing composite scores by more than 50 percent. The diagnostic utility of the classifier was validated on 65 consecutive transplant patients, resulting in an AUROC of 0.71 and a negative predictive value of 0.92-0.96. Differential expression analysis revealed a enrichment in inflammatory and immune pathways prior to PGD.

Conclusions: Pre-transplant level of KLKB1 is a robust predictor of post-transplant PGD. The combination with pre-transplant inotrope therapy enhances the prediction of PGD compared to pre-transplant KLKB1 levels alone and the resulting classifier equation validates within a prospective validation cohort. Inflammation and immune pathway enrichment characterize the pre-transplant proteomic signature predictive of PGD.
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http://dx.doi.org/10.1016/j.healun.2021.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464488PMC
October 2021

De Novo Human Leukocyte Antigen Allosensitization in Heartmate 3 Versus Heartmate II Left Ventricular Assist Device Recipients.

ASAIO J 2021 Apr 19. Epub 2021 Apr 19.

From the Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, New York Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, New York Division of Cardiothoracic Surgery, Department of Surgery, Columbia University Irving Medical Center, New York, New York.

Left ventricular assist devices (LVADs) are associated with the development of antihuman leukocyte antigen (HLA) antibodies, which can create a challenge for future transplantation in these patients. The differential effects of Heartmate 3 (HM3) versus Heartmate II (HMII) on de novo HLA allosensitization remain unknown. Patients who underwent HMII or HM3 implantation and had no prior HLA antibodies by solid-phase assay (Luminex) testing were included in this study. Complement-dependent cytotoxicity (CDC) panel reactive antibody (PRA) levels and Luminex antibody profiles were followed until cardiac transplantation, device explantation, or death. Electronic medical records were reviewed to examine posttransplant outcomes. Thirty-eight HM3 and 34 HMII patients with complete data were followed for 1.5 ± 1.1 years on device support. HM3 and HMII groups had similar age at implant, female gender, ischemic heart failure etiology, bridge strategy at implant, as well as intraoperative and postoperative transfusion requirements. 39.5% of HM3 and 47.1% of HMII patients developed detectable HLA antibodies by Luminex testing (p = 0.516). Development of high-level (mean fluorescence intensity >10,000) antibodies was significantly lower in HM3 than HMII patients (5.3 vs. 20.6%, p = 0.049). CDC PRA testing showed fewer HM3 patients with a positive result (PRA > 0%) than HMII patients (39.4 vs. 70.0%, p = 0.015). Among transplanted patients, those who had developed de novo sensitization on LVAD support showed a trend toward incidence of moderate to severe grade rejection compared with unsensitized patients (23.8 vs. 4.8%, p = 0.078). HM3 is associated with lower risk of de novo HLA sensitization compared with HMII.
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http://dx.doi.org/10.1097/MAT.0000000000001451DOI Listing
April 2021

T cell repertoire analysis suggests a prominent bystander response in human cardiac allograft vasculopathy.

Am J Transplant 2021 04 26;21(4):1465-1476. Epub 2020 Oct 26.

Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, New York.

T cells are implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), yet their clonality, specificity, and function are incompletely defined. Here we used T cell receptor β chain (TCRB) sequencing to study the T cell repertoire in the coronary artery, endomyocardium, and peripheral blood at the time of retransplant in four cases of CAV and compared it to the immunoglobulin heavy chain variable region (IGHV) repertoire from the same samples. High-dimensional flow cytometry coupled with single-cell PCR was also used to define the T cell phenotype. Extensive overlap was observed between intragraft and blood TCRBs in all cases, a finding supported by robust quantitative diversity metrics. In contrast, blood and graft IGHV repertoires from the same samples showed minimal overlap. Coronary infiltrates included CD4 and CD8 memory T cells expressing inflammatory (IFNγ, TNFα) and profibrotic (TGFβ) cytokines. These were distinguishable from the peripheral blood based on memory, activation, and tissue residency markers (CD45RO, CTLA-4, and CD69). Importantly, high-frequency rearrangements were traced back to endomyocardial biopsies (2-6 years prior). Comparison with four HLA-mismatched blood donors revealed a repertoire of shared TCRBs, including a subset of recently described cross-reactive sequences. These findings provide supportive evidence for an active local intragraft bystander T cell response in late-stage CAV.
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http://dx.doi.org/10.1111/ajt.16333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672660PMC
April 2021

Isolated Immunoglobulin G4-Related Disease Myocarditis Treated With Heart Transplantation.

Circ Heart Fail 2020 12 8;13(12):e007204. Epub 2020 Sep 8.

Beth Israel Deaconess Medical Center, Boston, MA (J.E.D., N.P.).

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007204DOI Listing
December 2020

United network for organ sharing outcomes after heart transplantation for al compared to ATTR cardiac amyloidosis.

Clin Transplant 2020 10 24;34(10):e14028. Epub 2020 Jul 24.

Center for Advanced Cardiac Care, Division of Cardiology, Columbia College of Physicians & Surgeons, New York, NY, USA.

Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients.
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http://dx.doi.org/10.1111/ctr.14028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744118PMC
October 2020

Desensitizing highly sensitized heart transplant candidates with the combination of belatacept and proteasome inhibition.

Am J Transplant 2020 12 7;20(12):3620-3630. Epub 2020 Jul 7.

Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA.

HLA antibodies pose a significant barrier to transplantation and current strategies to reduce allosensitization are limited. We hypothesized that augmenting proteasome inhibitor (PI) based desensitization with costimulation blockade (belatacept) to mitigate germinal center (GC) responses might increase efficacy and prevent rebound. Four highly sensitized (calculated panel reactive antibody [cPRA] class I and/or II >99%, complement-dependent cytotoxicity panel reactive antibody [CDC PRA+], C1q+) heart transplant candidates were treated with the combination of belatacept and PI therapy, which significantly reduced both class I and II HLA antibodies and increased the likelihood of identifying an acceptable donor. Three negative CDC crossmatches were achieved against 3, 6, and 8 donor-specific antibodies (DSA), including those that were historically C1q+ binding. Posttransplant, sustained suppression of 3 of 3, 4 of 6, and 8 of 8 DSA (cases 1-3) was achieved. Analysis of peripheral blood mononuclear cells before and after desensitization in one case revealed a decrease in naïve and memory B cells and a reduction in T follicular helper cells with a phenotype suggesting recent GC activity (CD38, PD1, and ICOS). Furthermore, a shift in the natural killer cell phenotype was observed with features suggestive of activation. Our findings support synergism between PI based desensitization and belatacept facilitating transplantation with a negative CDC crossmatch against historically strong, C1q binding antibodies.
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http://dx.doi.org/10.1111/ajt.16113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366746PMC
December 2020

Gut microbial diversity, inflammation, and oxidative stress are associated with tacrolimus dosing requirements early after heart transplantation.

PLoS One 2020 29;15(5):e0233646. Epub 2020 May 29.

Division of Cardiology, Department of Medicine, NewYork-Presbyterian Hospital, Columbia University, New York, New York, United States of America.

Introduction: Effective tacrolimus (TAC) dosing is hampered by complex pharmacokinetics and significant patient variability. The gut microbiome, a key mediator of endotoxemia, inflammation and oxidative stress in advanced heart failure (HF) patients, is a possible contributor to interindividual variations in drug efficacy. The effect of alterations in the gut microbiome on TAC dosing requirements after heart transplant (HT) has not been explored.

Methods: We enrolled 24 patients (mean age = 55.8 ±2.3 years) within 3 months post-HT. Biomarkers of endotoxemia ((lipopolysaccharide (LPS)), inflammation (tumor necrosis factor-α (TNF-α)) and oxidative stress (8,12-iso-Isoprostane F-2alpha-VI) were measured in 16 blood samples. 22 stool samples were analyzed using 16S rRNA sequencing. TAC dose and serum trough level were measured at the time of stool and blood collection. TAC doses were reported in mg/kg/day and as level-to-dose (L/D) ratio, and categorized as ≤ vs. > median.

Results: The median TAC dose was 0.1 mg/kg/day and L/D ratio was 100.01. Above the median daily weight-based TAC dose was associated with higher gut microbial alpha diversity (p = 0.03); similarly, TNF-α and 8,12-iso-Isoprostane F-2alpha-VI levels were lower and LPS levels were higher in the above median TAC group, although these findings were only marginally statistically significant and dependent on BMI adjustment. We observed n = 37 taxa to be significantly enriched among patients with > median TAC dose (all FDR<0.05), several of which are potential short-chain fatty acid producers with anti-inflammatory properties, including taxa from the family Subdoligranulum.

Conclusions: Our pilot study observed gut microbial alpha diversity to be increased while inflammation and oxidative stress were reduced among patients requiring higher TAC doses early after HT.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233646PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259664PMC
August 2020

Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019.

JAMA Cardiol 2020 10;5(10):1165-1169

Division of Cardiology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York.

Importance: Recipients of heart transplant (HT) may be at increased risk of adverse outcomes attributable to infection with coronavirus disease 2019 (COVID-19) because of multiple comorbidities and clinically significant immunosuppression.

Objective: To describe the characteristics, treatment, and outcomes of recipients of HT with COVID-19.

Design, Setting, And Participants: This case series from a single large academic heart transplant program in New York, New York, incorporates data from between March 1, 2020, and April 24, 2020. All recipients of HT followed up by this center who were infected with COVID-19 were included.

Interventions: Heart transplant and a confirmed diagnosis of COVID-19.

Main Outcomes And Measures: The primary measure was vital status at end of study follow-up. Secondary measures included patient characteristics, laboratory analyses, changes to immunosuppression, and treatment administered for COVID-19.

Results: Twenty-eight patients with HT received a confirmed diagnosis of COVID-19. The median age was 64.0 (interquartile range [IQR], 53.5-70.5) years, 22 (79%) were men, and the median time from HT was 8.6 (IQR, 4.2-14.5) years. Comorbid conditions included hypertension in 20 patients (71%), diabetes in 17 patients (61%), and cardiac allograft vasculopathy in 16 patients (57%). Twenty-two participants (79%) were admitted for treatment, and 7 (25%) required mechanical ventilation. Most (13 of 17 [76%]) had evidence of myocardial injury (median high-sensitivity troponin T, 0.055 [IQR, 0.0205-0.1345] ng/mL) and elevated inflammatory biomarkers (median peak high-sensitivity C-reactive protein, 11.83 [IQR, 7.44-19.26] mg/dL; median peak interleukin 6, 105 [IQR, 38-296] pg/mL). Among patients managed at the study institution, mycophenolate mofetil was discontinued in 16 patients (70%), and 6 (26%) had a reduction in the dose of their calcineurin inhibitor. Treatment of COVID-19 included hydroxychloroquine (18 patients [78%]), high-dose corticosteroids (8 patients [47%]), and interleukin 6 receptor antagonists (6 patients [26%]). Overall, 7 patients (25%) died. Among 22 patients (79%) who were admitted, 11 (50%) were discharged home, 4 (18%) remain hospitalized at the end of the study, and 7 (32%) died during hospitalization.

Conclusions And Relevance: In this single-center case series, COVID-19 infection was associated with a case fatality rate of 25% in recipients of HT. Immunosuppression was reduced in most of this group of patients. Further study is required to evaluate the optimal approach to management of COVID-19 infection in the HT population.
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http://dx.doi.org/10.1001/jamacardio.2020.2159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221850PMC
October 2020

Profiling non-HLA antibody responses in antibody-mediated rejection following heart transplantation.

Am J Transplant 2020 09 26;20(9):2571-2580. Epub 2020 Apr 26.

Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, New York, USA.

Antibody-mediated rejection (AMR) driven by the development of donor-specific antibodies (DSA) directed against mismatched donor human leukocyte antigen (HLA) is a major risk factor for graft loss in cardiac transplantation. Recently, the relevance of non-HLA antibodies has become more prominent as AMR can be diagnosed in the absence of circulating DSA. Here, we assessed a single-center cohort of 64 orthotopic heart transplant recipients transplanted between 1994 and 2014. Serum collected from patients with ≥ pAMR1 (n = 43) and non-AMR (n = 21) were tested for reactivity against a panel of 44 non-HLA autoantigens. The AMR group had a significantly greater percentage of patients with elevated reactivity to autoantigens compared to non-AMR (P = .002) and healthy controls (n = 94, P < .0001). DSA-positive AMR patients exhibited greater reactivity to autoantigens compared to DSA-negative (P < .0001) and AMR patients with DSA and PRA > 10% were identified as the subgroup with significantly elevated responses. Reactivity to 4 antigens, vimentin, beta-tubulin, lamin A/C, and apolipoprotein L2, was significantly different between AMR and non-AMR patients. Moreover, increased reactivity to these antigens was associated with graft failure. These results suggest that antibodies to non-HLA are associated with DSA-positive AMR although their specific role in mediating allograft injury is not yet understood.
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http://dx.doi.org/10.1111/ajt.15871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117249PMC
September 2020

Discontinuing amiodarone treatment prior to heart transplantation lowers incidence of severe primary graft dysfunction.

Clin Transplant 2020 02 29;34(2):e13779. Epub 2020 Jan 29.

Division of Cardiac Surgery, Department of Surgery, Columbia University Medical Center, New York, New York.

Background: Recent studies have shown an increased incidence of primary graft dysfunction (PGD) in patients treated with amiodarone prior to orthotopic heart transplant (OHT). We hypothesized that discontinuation of amiodarone before OHT may lower the incidence of severe PGD.

Methods: This was a single-center retrospective study of 381 adult OHT recipients between January 2010 and June 2017. Within 6 months prior to OHT, 197 did not receive amiodarone (Group 1), 142 continued amiodarone to OHT (Group 2), and 42 had amiodarone treatment discontinued before OHT (Group 3).

Results: 53 (13.9%) participants developed severe PGD, 13 (6.6%) of which were in Group 1, 36 (25.4%) were in Group 2, and 4 (9.5%) were in Group 3 (P < .001). Multivariable analysis revealed continued amiodarone treatment to OHT (Group 2; OR, 3.70; 95% CI, 1.26-10.88; P = .018) to be an independent risk factor for the development of severe PGD when Group 1 served as the reference group. Moreover, patients in Group 3 had no difference in the risk of severe PGD (OR = 0.416, 95% CI = 0.08-2.15; P = .296).

Conclusion: We found that discontinuing amiodarone treatment prior to OHT resulted a lower incidence of severe PGD.
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http://dx.doi.org/10.1111/ctr.13779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055534PMC
February 2020

Left ventricular decompression on Veno-arterial extracorporeal membrane oxygenation with intra-aortic balloon Counterpulsation.

J Cardiothorac Surg 2019 Aug 22;14(1):153. Epub 2019 Aug 22.

Columbia University Irving Medical Center, 173 Fort Washington Avenue, Room 4617, 630 West 168th St, New York, NY, 10032, USA.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used increasingly to support patients with cardiogenic shock (CS). There has been growing recognition of the favorable and unfavorable hemodynamic effects of this therapy and recent interest in the use of other percutaneous circulatory support devices to offset some of the potentially harmful hemodynamic effects. Herein, we provide visual evidence of the effects of intra-aortic balloon pump (IABP) counterpulsation for a patient with peripheral VA-ECMO cannulation.

Case Presentation: A 68 year old man who had undergone orthotopic heart transplantation presented with 2 days of fatigue, orthopnea, and paroxysmal nocturnal dyspnea. On examination, he was tachycardic, hypotensive and hypoxic with cool extremities, consistent with CS. Transthoracic echocardiogram (TTE) showed new severe biventricular dysfunction with a left ventricular ejection fraction of 15%, right heart catheterization demonstrated elevated filling pressures and low output. An IABP was inserted via the left femoral artery with minimal improvement in hemodynamics. He was escalated to VA-ECMO. Repeat TTE demonstrated aortic valve (AV) opening with each cardiac cycle and mild MR. With placement of the IABP on standby Additional file 1: Video 1 (video 0:03), the AV no longer opened. Re-initiation of balloon counterpulsation resulted in resumed AV opening with each beat Additional file 1: Video 1 (video 0:17). He was treated for presumed acute allograft rejection with methylprednisolone, thymoglobulin, intravenous immunoglobulin and plasmapheresis with improvement in allograft function. However, he developed an Enterobacter aerogenes pneumonia and rapidly fatal septic shock.

Conclusions: This case visually demonstrates effective LV decompression by IABP counterpulsation in VA-ECMO support. While the overall effects of LV decompression in patients on VA-ECMO with IABP are still unclear, this report demonstrates one potential mechanism of benefit in the prevention of stagnation of blood flow that may lead to intra-cardiac or aortic root thrombus formation.
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http://dx.doi.org/10.1186/s13019-019-0970-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704520PMC
August 2019

Desensitization in the Era of Precision Medicine: Moving From the Bench to Bedside.

Transplantation 2019 08;103(8):1574-1581

Department of Surgery, University of Chicago, Chicago, IL.

Patients with antibodies to HLA wait longer for transplant and are at increased risk of adverse outcomes. For more than a decade, drug therapy approaches have been tested to modulate the immune system to prevent or reduce donor-specific antibody levels. Despite some studies reporting success in facilitating transplant, many patients do not respond or experience donor-specific antibody rebound, highlighting the diversity of the individual patient's immune response. While advances in immunomodulatory therapies have resulted in escalating efforts to successfully treat highly sensitized patients, further insight into the human immune system has uncovered its enormous complexity and diversity calling for a personalized approach. Yet, even defining the sensitized transplant candidate can be troublesome and much remains to be understood about the interaction between an individual's immune system as a whole and their response to our current desensitization strategies. The shift toward a personalized approach calls for a reevaluation of what we know and what remains to be determined; a process that will require iterative translational approaches. This review will focus on new insights into how the interaction between immune risk assessment, the patient's immunological history, and the clinical context can be reconciled to develop a precision-based approach to pretransplant management.
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http://dx.doi.org/10.1097/TP.0000000000002737DOI Listing
August 2019

Impact of Bridge to Transplantation With Continuous-Flow Left Ventricular Assist Devices on Posttransplantation Mortality.

Circulation 2019 08 17;140(6):459-469. Epub 2019 Jun 17.

Division of Cardiology, Department of Medicine (M.A.F., A.R.G., R.G., S.W.R., F.L., V.K.T.), Columbia University College of Physicians and Surgeons, New York, NY.

Background: Bridge to transplantation (BTT) with left ventricular assist devices (LVADs) is a mainstay of therapy for heart failure in patients awaiting heart transplantation (HT). Criteria for HT listing do not differ between patients medically managed and those mechanically bridged to HT. The objectives of the present study were to evaluate the impact of BTT with LVAD on posttransplantation survival, to describe differences in causes of 1-year mortality in medically and mechanically bridged patients, and to evaluate differences in risk factors for 1-year mortality between those with and those without LVAD at the time of HT.

Methods: Using the United Network of Organ Sharing database, we identified 5486 adult, single-organ HT recipients transplanted between 2008 and 2015. Patients were propensity matched for likelihood of LVAD at the time of HT. Kaplan-Meier survival estimates were used to assess the impact of BTT on 1- and 5-year mortality. Logistic regression analysis was used to evaluate the odds ratio of 1-year mortality for patients BTT with LVAD compared with those with medical management across clinically significant variables at various thresholds.

Results: Early mortality was higher in mechanically bridged patients: 9.5% versus 7.2% mortality at 1 year (P<0.001). BTT patients incurred an increased risk of 1-year mortality with an estimated glomerular filtration rate of 40 to 60 mL·min·1.73 m (odds ratio, 1.69; P=0.003) and <40 mL·min·1.73 m (odds ratio, 2.16; P=0.005). A similar trend was seen in patients with a body mass index of 25 to 30 kg/m (odds ratio, 1.88; P=0.024) and >30 kg/m (odds ratio, 2.11; P<0.001). When patients were stratified by BTT status and the presence of risk factors, including age >60 years, estimated glomerular filtration rate <40 mL·min·1.73 m, and body mass index >30 kg/m, there were significant differences in 1-year mortality between medium- and high-risk medically and mechanically bridged patients, with 1-year mortality in high-risk BTT patients at 17.6% compared with 10.4% in high-risk medically managed patients.

Conclusions: Bridge to HT with LVAD, although necessary because of organ scarcity and capable of improving wait list survival, confers a significantly higher risk of early posttransplantation mortality. Patients bridged with mechanical support may require more careful consideration for transplant eligibility after LVAD placement.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223200PMC
August 2019

Extracorporeal membrane oxygenation for primary graft dysfunction after heart transplant.

J Thorac Cardiovasc Surg 2019 12 28;158(6):1576-1584.e3. Epub 2019 Feb 28.

Division of Cardiothoracic Surgery, Department of Surgery, Columbia University Medical Center, New York, NY. Electronic address:

Objective: Venoarterial extracorporeal membrane oxygenation is a useful treatment for severe primary graft dysfunction after heart transplant. The ideal timing of initiation is unknown.

Methods: We retrospectively reviewed 362 adult heart transplant recipients at our center between January 2011 and December 2017. Thirty-eight patients (10.5%) experienced severe primary graft dysfunction treated with venoarterial extracorporeal membrane oxygenation. As our institution adopted a prompt venoarterial extracorporeal membrane oxygenation policy in 2015, patients were stratified into pre-2015 (conservative extracorporeal membrane oxygenation: n = 18) and post-2015 (prompt extracorporeal membrane oxygenation: n = 20) cohorts. Clinical outcomes were compared.

Results: Baseline characteristics were similar (conservative vs prompt) except for age (51.82 vs 59.96 years, P = .036), aspartate transaminase (32 vs 21.5 U/L, P = .038), male donor (44.4 vs 80%, P = .042), and donor ejection fraction (60 vs 65%, P = .047). Median ischemic time was significantly longer in the conservative extracorporeal membrane oxygenation cohort (210 vs 148 minutes, P = .005). Median time to initiation of extracorporeal membrane oxygenation was significantly shorter in the prompt extracorporeal membrane oxygenation cohort (7.26 vs 1.95 hours, P < .0001). There was no difference in intensive care unit stay or major complications. In-hospital mortality improved from 28% (conservative) to 5% (prompt, P = .083). Post-transplant survival at 1 year was 67% in the conservative extracorporeal membrane oxygenation cohort and 90% in the prompt extracorporeal membrane oxygenation cohort (P = .117). There was no difference in the Kaplan-Meier survival curves (P = .071), although Cox regression suggested, but certainly did not prove, a 74.6% lower risk of mortality in the prompt extracorporeal membrane oxygenation group (P = .094).

Conclusions: Prompt venoarterial extracorporeal membrane oxygenation use for primary graft dysfunction after heart transplant results in excellent myocardial recovery and a possible decrease in mortality without increased risk of complications.
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http://dx.doi.org/10.1016/j.jtcvs.2019.02.065DOI Listing
December 2019

Management of primary graft failure after heart transplantation: Preoperative risks, perioperative events, and postoperative decisions.

Clin Transplant 2019 06 23;33(6):e13557. Epub 2019 Apr 23.

Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, New York.

Primary graft failure (PGF) after heart transplantation (HT) is a devastating and unexpected event characterized by failure of the graft to adequately support recipient circulation necessitating high doses of vasopressors and inotropes and/or temporary mechanical circulatory support. Although it represents an increasingly common event in the current era, there remains a high degree of variability in prevalence, reported risk factors, and approach to this clinical entity. The purpose of the current review is to highlight preoperative considerations including known incidence and risk factors, perioperative issues involving the identification and management of PGF, and postoperative decisions related to weaning of mechanical circulatory support and titration of immunosuppressive therapy. Lastly, we highlight future directions in PGF research, involving basic and translational research, that have the potential to uncover novel strategies of risk stratification and treatment. CASE: Our patient is a 53-year-old man with end-stage non-ischemic dilated cardiomyopathy complicated by ventricular tachycardia (VT), post-capillary pulmonary hypertension, and renal insufficiency. After progressing to NYHA Class IV symptoms, he underwent implantation of a durable left ventricular assist device (LVAD) as bridge to transplant (BTT). On device support, he developed recurrent VT resulting in multiple defibrillator discharges and hospital admission for intravenous anti-arrhythmic therapy. He is subsequently upgraded to a higher status on the waiting list. A suitable donor is identified, with an appropriate predicted heart mass and an anticipated ischemic time of <4 hours. He is taken to the operating room, where at the time of anesthesia induction he develops vasodilatory shock, requiring high-dose vasopressors, and cardiopulmonary bypass (CPB) support for dissection. After surgical anastomosis, cross clamp removal and reperfusion, graft function is extremely poor, there is significant bradycardia requiring pacing, and the patient is unable to be weaned successfully from CPB. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is initiated, and the patient is transferred to the intensive care unit. Retrospective flow crossmatch is negative. This patient is suffering from severe primary graft failure.
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http://dx.doi.org/10.1111/ctr.13557DOI Listing
June 2019

Prior Amiodarone Exposure Reduces Tacrolimus Dosing Requirements in Heart Transplant Recipients.

Prog Transplant 2019 06 7;29(2):129-134. Epub 2019 Mar 7.

1 Department of Pharmacy, NewYork-Presbyterian Hospital, New York, NY, USA.

Introduction: Amiodarone use prior to heart transplant is independently associated with a higher rate of severe primary graft dysfunction and in-hospital mortality. Amiodarone may also alter the pharmacokinetics of medications metabolized via cytochrome P450. No data exist regarding the interaction between pretransplant amiodarone and tacrolimus concentrations.

Design: Single-center retrospective study of transplant patients between January 1, 2014, and June 30, 2016. A therapeutic tacrolimus concentration was defined as a trough level between 8 and 15 ng/mL for 2 consecutive days. The primary outcome was the tacrolimus therapeutic weight-based dosing requirements (mg/kg/day) for patients receiving amiodarone prior to transplant when compared to those without prior receipt of amiodarone. Secondary outcomes include the incidence of cellular rejection and mortality within 6 months posttransplant.

Results: Multi-organ transplant recipients (n = 3), retransplants (n = 9), those who died prior to a therapeutic level (n = 1), and those receiving amiodarone posttransplant (n = 7) were excluded from the analysis. Of the 80 patients included, 34 (42%) received amiodarone prior to transplant. Patient characteristics were similar, with the exception of primary graft dysfunction incidence (38% in amiodarone vs 8.5% in control, P = .001). The median therapeutic dose was 0.1 (interquartile range [IQR]: 0.07-0.12) versus 0.13 (IQR: 0.09-0.17) in the amiodarone and control groups, respectively, ( P < .01). No significant difference in mortality or rejection was noted.

Conclusion: Patients receiving amiodarone prior to transplant require a lower weight-based dose of tacrolimus.
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http://dx.doi.org/10.1177/1526924819835840DOI Listing
June 2019

Providers' Perspectives on Sharing Health Information through Acute Care Patient Portals.

AMIA Annu Symp Proc 2018 5;2018:1273-1281. Epub 2018 Dec 5.

Department of Biomedical Informatics, Columbia University, New York, NY.

Engaging healthcare providers in acute care patient portal implementation is critical to ensure productive use. However, few studies have assessed provider's perceptions of an acute care portal after implementation. In this study, we surveyed 63 nurses, physicians, and physician assistants following a 3-year randomized trial of an acute care portal. The survey assessed providers' perceptions of the portal and its impact on care delivery. Respondents reported that the portal positively impacted care, and they perceived that their patients found it usable and trustworthy. Respondents reported that all the portal's features were useful, especially the display of laboratory test results. Compared with the results of a patient survey, providers underestimated the portal's usefulness to patients, and ranked features as significantly less often than patients (57% vs. 74%; p<0.001). Our study found that providers supported their patients' use of the portal, but may have underappreciated the portal's value to patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371328PMC
January 2020

Technology Access, Technical Assistance, and Disparities in Inpatient Portal Use.

Appl Clin Inform 2019 01 16;10(1):40-50. Epub 2019 Jan 16.

Department of Biomedical Informatics, Columbia University, New York, New York, United States.

Background: Disadvantaged populations, including minorities and the elderly, use patient portals less often than relatively more advantaged populations. Limited access to and experience with technology contribute to these disparities. Free access to devices, the Internet, and technical assistance may eliminate disparities in portal use.

Objective: To examine predictors of versus portal use among hospitalized patients who received free access to an iPad, the Internet, and technical assistance.

Materials And Methods: This subgroup analysis includes 146 intervention-arm participants from a pragmatic randomized controlled trial of an inpatient portal. The participants received free access to an iPad and inpatient portal while hospitalized on medical and surgical cardiac units, together with hands-on help using them. We used logistic regression to identify characteristics predictive of use.

Results: More technology experience (adjusted odds ratio [OR] = 5.39,  = 0.049), less severe illness (adjusted OR = 2.07,  = 0.077), and private insurance (adjusted OR = 2.25,  = 0.043) predicted use, with a predictive performance (area under the curve) of 65.6%. No significant differences in age, gender, race, ethnicity, level of education, employment status, or patient activation existed between the and users in bivariate analyses. Significantly more users noticed medical errors during their hospital stay.

Discussion And Conclusion: Portal use was not associated with several sociodemographic characteristics previously found to limit use in the inpatient setting. However, limited technology experience and high illness severity were still barriers to use. Future work should explore additional strategies, such as enrolling health care proxies and improving usability, to reduce potential disparities in portal use.
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http://dx.doi.org/10.1055/s-0038-1676971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335107PMC
January 2019

Engaging hospitalized patients with personalized health information: a randomized trial of an inpatient portal.

J Am Med Inform Assoc 2019 02;26(2):115-123

Department of Biomedical Informatics, Columbia University, New York, New York, USA.

Objective: To determine the effects of an inpatient portal intervention on patient activation, patient satisfaction, patient engagement with health information, and 30-day hospital readmissions.

Methods And Materials: From March 2014 to May 2017, we enrolled 426 English- or Spanish-speaking patients from 2 cardiac medical-surgical units at an urban academic medical center. Patients were randomized to 1 of 3 groups: 1) usual care, 2) tablet with general Internet access (tablet-only), and 3) tablet with an inpatient portal. The primary study outcome was patient activation (Patient Activation Measure-13). Secondary outcomes included all-cause readmission within 30 days, patient satisfaction, and patient engagement with health information.

Results: There was no evidence of a difference in patient activation among patients assigned to the inpatient portal intervention compared to usual care or the tablet-only group. Patients in the inpatient portal group had lower 30-day hospital readmissions (5.5% vs. 12.9% tablet-only and 13.5% usual care; P = 0.044). There was evidence of a difference in patient engagement with health information between the inpatient portal and tablet-only group, including looking up health information online (89.6% vs. 51.8%; P < 0.001). Healthcare providers reported that patients found the portal useful and that the portal did not negatively impact healthcare delivery.

Conclusions: Access to an inpatient portal did not significantly improve patient activation, but it was associated with looking up health information online and with a lower 30-day hospital readmission rate. These results illustrate benefit of providing hospitalized patients with real-time access to their electronic health record data while in the hospital.

Trial Registration: ClinicalTrials.gov Identifier: NCT01970852.
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http://dx.doi.org/10.1093/jamia/ocy146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339515PMC
February 2019

Engaging hospital patients in the medication reconciliation process using tablet computers.

J Am Med Inform Assoc 2018 11;25(11):1460-1469

Department of Biomedical Informatics, Columbia University, New York, New York, USA.

Objective: Unintentional medication discrepancies contribute to preventable adverse drug events in patients. Patient engagement in medication safety beyond verbal participation in medication reconciliation is limited. We conducted a pilot study to determine whether patients' use of an electronic home medication review tool could improve medication safety during hospitalization.

Materials And Methods: Patients were randomized to use a tool before or after hospital admission medication reconciliation to review and modify their home medication list. We assessed the quantity, potential severity, and potential harm of patients' and clinicians' medication changes. We also surveyed clinicians to assess the tool's usefulness.

Results: Of 76 patients approached, 65 (86%) participated. Forty-eight (74%) made changes to their home medication list [before: 29 (81%), after: 19 (66%), p = .170]. Before group participants identified 57 changes that clinicians subsequently missed on admission medication reconciliation. Thirty-nine (74%) had a significant or greater potential severity, and 19 (36%) had a greater than 50-50 chance of harm. After group patients identified 68 additional changes to their reconciled medication lists. Fifty-one (75%) had a significant or greater potential severity, and 33 (49%) had a greater than 50-50 chance of harm. Clinicians reported believing that the tool would save time, and patients would supply useful information.

Discussion: The results demonstrate a high willingness of patients to engage in medication reconciliation, and show that patients were able to identify important medication discrepancies and often changes that clinicians missed.

Conclusion: Engaging patients in admission medication reconciliation using an electronic home medication review tool may improve medication safety during hospitalization.
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http://dx.doi.org/10.1093/jamia/ocy115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263785PMC
November 2018

Sharing Clinical Notes with Hospitalized Patients via an Acute Care Portal.

AMIA Annu Symp Proc 2017 16;2017:800-809. Epub 2018 Apr 16.

Value Institute, NewYork-Presbyterian Hospital, New York, NY.

Though several institutions offer hospitalized patients access to their medical records through acute care patient portals, no studies have assessed the potential impact of patients' access to physicians' notes through these systems. We employed a mixed-methods approach, including patient surveys, system usage log analysis, and qualitative interviews, to describe patients' perspectives on receiving their clinical notes and usage of the clinical notes feature in an acute care patient portal. Patients visited the clinical notes feature more frequently and for longer durations than any other feature. In qualitative interviews, patients reported improved access to information, better insight into their conditions, decreased anxiety, increased appreciation for clinicians, improvements in health behaviors, and more engagement in care. Our results suggest that sharing notes with hospitalized patients is feasible and beneficial, although further studies should investigate the magnitude of benefit and explore the unintended negative consequences associated with increased transparency of clinical information.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977594PMC
March 2019

Mechanical Circulatory Support Device Utilization and Heart Transplant Waitlist Outcomes in Patients With Restrictive and Hypertrophic Cardiomyopathy.

Circ Heart Fail 2018 03;11(3):e004665

From the Division of Cardiology, Department of Medicine (L.S., B.W., L.K.T., F.L., S.R., P.C.C., M.M., M.J.F., V.K.T.) and Division of Cardiac Surgery, Department of Surgery (K.T., H.T., Y.N.), Columbia University College of Physicians and Surgeons, New York, NY.

Background: Patients with restrictive cardiomyopathy (RCM) and hypertrophic cardiomyopathy (HCM) generally are considered poor candidates for mechanical circulatory support devices (MCSDs) and often not able to be bridged mechanically to heart transplantation. This study characterized MCSD utilization and transplant waitlist outcomes in patients with RCM/HCM under the current allocation system and discusses changes in the era of the new donor allocation system.

Methods And Results: Patients waitlisted from 2006 to 2016 in the United Network for Organ Sharing registry were stratified by RCM/HCM versus other diagnoses. MCSD utilization and waitlist duration were analyzed by propensity score models. Waitlist outcomes were assessed by cumulative incidence functions with competing events. Predictors of waitlist mortality or delisting for worsening status in patients with RCM/HCM were identified by proportional hazards model. Of 30 608 patients on the waitlist, 5.1% had RCM/HCM. Patients with RCM/HCM had 31 fewer waitlist days (<0.01) and were ≈26% less likely to receive MCSD (<0.01). Cumulative incidence of waitlist mortality was similar between cohorts; however, patients with RCM/HCM had higher incidence of heart transplantation. Predictors of waitlist mortality or delisting for worsening status in patients with RCM/HCM without MCSD support included estimated glomerular filtration rate <60 mL/min per 1.73 m, pulmonary capillary wedge pressure >20 mm Hg, inotrope use, and subjective frailty.

Conclusions: Patients with RCM/HCM are less likely to receive MCSD but have similar waitlist mortality and slightly higher incidence of transplantation compared with other patients. The United Network for Organ Sharing RCM/HCM risk model can help identify patients who are at high risk for clinical deterioration and in need of expedited heart transplantation.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905429PMC
March 2018

Socioeconomic Disparities in Adherence and Outcomes After Heart Transplant: A UNOS (United Network for Organ Sharing) Registry Analysis.

Circ Heart Fail 2018 03;11(3):e004173

From the Division of Cardiology, Department of Medicine (B.W., A.C., R.C.G., F.L., S.R., M.A.F., P.C.C., V.K.T.) and Division of Cardiothoracic Surgery, Department of Surgery (K.T., H.T., Y.N.), Columbia University College of Physicians and Surgeons, New York, NY.

Background: There is mixed evidence of racial and socioeconomic disparities in heart transplant outcomes. Their underlying cause-and whether individual- or community-level traits are most influential-remains unclear. The current study aimed to characterize socioeconomic disparities in outcomes and identify time trends and mediators of these disparities.

Methods And Results: We used United Network for Organ Sharing registry data and included 33 893 adult heart transplant recipients between 1994 and 2014. Socioeconomic status (SES) indicators included insurance, education, and neighborhood SES measured using a composite index. Black race and multiple indicators of low SES were associated with the primary outcome of death or retransplant, independent of baseline clinical characteristics. Blacks had lower HLA and race matching, but further adjustment for these and other graft characteristics only slightly attenuated the association with black race (HR, 1.25 after adjustment). This and the associations with neighborhood SES (HR, 1.19 for lowest versus highest decile), Medicare (HR, 1.17), Medicaid (HR, 1.29), and college education (HR, 0.90) remained significant after full adjustment. When comparing early (1994-2000) and late (2001-2014) cohorts, the disparities associated with the middle (second and third) quartiles significantly decreased over time, but those associated with lowest SES quartile and black race persisted. Low neighborhood SES was also associated with higher risks of noncompliance (HR, 1.76), rejection (HR, 1.28), hospitalization (HR, 1.13), and infection (HR, 1.10).

Conclusions: Racial and socioeconomic disparities exist in heart transplant outcomes, but the latter may be narrowing over time. These disparities are not explained by differences in clinical or graft characteristics.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004173DOI Listing
March 2018

Outcomes associated with mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients: A meta-analysis.

Int J Cardiol 2018 Aug 24;265:71-76. Epub 2018 Mar 24.

Department of Pharmacy Practice, University of Connecticut, Storrs, CT, United States.

Background: Data evaluating mTOR inhibitor use heart transplant (HT) patients comes from relatively small studies and controversy exists regarding their specific role. We performed a meta-analysis of randomized trials to evaluate the efficacy and safety of mTOR inhibitors in HT patients.

Methods: We performed a systematic literature search of Medline and Embase through July 2017 identifying studies evaluating mTOR inhibitors in HT patients reporting effects on coronary allograft vasculopathy (CAV), renal function, acute cellular rejection (ACR), cytomegalovirus (CMV) infection, and discontinuation due to adverse drug events (ADE). Data were pooled using a random-effects model producing a mean difference (MD; for continuous data) or odds ratio (OR; for dichotomous data) and 95% confidence interval (CI).

Results: 14 trials reported at least one outcome of interest. Change in mean maximal intimal thickness was significantly reduced with mTOR (-0.04 [-0.07 to -0.02]) compared to calcineurin inhibitor/mycophenolate mofetil (CNI/MMF). Rates of CMV infection were also significantly reduced (0.26; [0.2 to 0.32]) with mTOR regimens compared to CNI/MMF therapy. ACR was more frequent with CNI-sparing regimens 6.46 [1.55 to 26.95]). eGFR was significantly improved with CNI-sparing therapies (mean difference 12.09 mL/min [2.43 to 21.74]), but was similar between CNI/mTOR versus CNI/MMF regimens (p > 0.05). Rates of discontinuation due to ADE were higher in mTOR-containing regimens (OR 2.15 [1.28 to 3.60], p = 0.01), while mortality rates were similar (OR 0.91 [0.61 to 1.37], p = 0.62).

Conclusions: mTOR-containing regimens can attenuate CAV and CMV risk in HT recipients. A mTOR/MMF combination preserves renal function but increases the risk of ACR.
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http://dx.doi.org/10.1016/j.ijcard.2018.03.111DOI Listing
August 2018

Comparative Assessment of Anti-HLA Antibodies Using Two Commercially Available Luminex-Based Assays.

Transplant Direct 2017 Nov 2;3(11):e218. Epub 2017 Oct 2.

Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY.

Background: Allospecific anti-HLA antibodies (Abs) are associated with rejection of solid organ grafts. The 2 main kits to detect anti-HLA Ab in patient serum are commercialized by Immucor and One Lambda/ThermoFisher. We sought to compare the performance of both platforms.

Methods: Background-adjusted mean fluorescence intensity (MFI) values were used from both platforms to compare sera collected from 125 pretransplant and posttransplant heart and lung transplant recipients.

Results: Most HLA class I (94.5%) and HLA class II (89%) Abs with moderate to high MFI titer (≥4000) were detected by both assays. A modest correlation was observed between MFI values obtained from the 2 assays for both class I ( = 0.3, = 0.09, < 0.0001) and class II Ab ( = 0.707, = 0.5, < 0.0001). Both assays detected anti-class I and II Ab that the other did not; however, no specific HLA allele was detected preferentially by either of the 2 assays. For a limited number of discrepant sera, dilution resulted in comparable reactivity profiles between the 2 platforms.

Conclusions: Immucor and One Lambda/ThermoFisher assays have a similar, albeit nonidentical, ability to detect anti-HLA Ab. Although the correlation between the assays was present, significant variances exist, some of which can be explained by a dilution-sensitive "prozone" effect.
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http://dx.doi.org/10.1097/TXD.0000000000000734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682763PMC
November 2017
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