Hannah A Valantine

Stanford University, Palo Alto, California, United States

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Publications (195)1238.64 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores. We determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race. In 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p < 0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels. African Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.
    The Journal of Heart and Lung Transplantation 02/2015; DOI:10.1016/j.healun.2015.01.987 · 5.61 Impact Factor
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    ABSTRACT: Monitoring allograft health is an important component of posttransplant therapy. Endomyocardial biopsy is the current gold standard for cardiac allograft monitoring but is an expensive and invasive procedure. Proof of principle of a universal, noninvasive diagnostic method based on high-throughput screening of circulating cell-free donor-derived DNA (cfdDNA) was recently demonstrated in a small retrospective cohort. We present the results of a prospective cohort study (65 patients, 565 samples) that tested the utility of cfdDNA in measuring acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (mean depth, 1.2 giga-base pairs) to quantify the fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, we demonstrate that cfdDNA enables diagnosis of acute rejection after heart transplantation, with an area under the receiver operating characteristic curve of 0.83 and sensitivity and specificity that are comparable to the intrinsic performance of the biopsy itself. This noninvasive genome transplant dynamics approach is a powerful and informative method for routine monitoring of allograft health without incurring the risk, discomfort, and expense of an invasive biopsy.
    Science translational medicine 06/2014; 6(241):241ra77. DOI:10.1126/scitranslmed.3007803 · 14.41 Impact Factor
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    ABSTRACT: Purpose To assess whether the proportion of women faculty, especially at the full professor rank, increased from 2004 to 2010 at Stanford University School of Medicine after a multifaceted intervention. Method The authors surveyed gender composition and faculty satisfaction five to seven years after initiating a multifaceted intervention to expand recruitment and development of women faculty. The authors assessed pre/post relative change and rates of increase in women faculty at each rank, and faculty satisfaction; and differences in pre/post change and estimated rate of increase between Stanford and comparator cohorts (nationally and at peer institutions). Results Post intervention, women faculty increased by 74% (234 to 408), with assistant, associate, and full professors increasing by 66% (108 to 179), 87% (74 to 138), and 75% (52 to 91), respectively. Nationally and at peer institutions, women faculty increased by about 30% (30,230 to 39,200 and 4,370 to 5,754, respectively), with lower percentages at each rank compared with Stanford. Estimated difference (95% CI) in annual rate of increase was larger for Stanford versus the national cohort: combined ranks 0.36 (0.17 to 0.56), P = .001; full professor 0.40 (0.18 to 0.62), P = .001; and versus the peer cohort: combined ranks 0.29 (0.07 to 0.51), P = .02; full professor 0.37 (0.14 to 0.60), P = .003. Stanford women faculty satisfaction increased from 48% (2003) to 71% (2008). Conclusions Increased satisfaction and proportion of women faculty, especially full professors, suggest that the intervention may ameliorate the gender gap in academic medicine.
    Academic medicine: journal of the Association of American Medical Colleges 06/2014; 89(6):904-11. DOI:10.1097/ACM.0000000000000245 · 3.47 Impact Factor
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S175. DOI:10.1016/j.healun.2014.01.472 · 5.61 Impact Factor
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S84-S85. DOI:10.1016/j.healun.2014.01.261 · 5.61 Impact Factor
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    ABSTRACT: Gene expression profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of gene expression profiling test scores within a patient may predict risk of future events of allograft dysfunction or death. Patients from the IMAGE study with rejection surveillance gene expression profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene expression profiling score variability was defined as the standard deviation of an individual's cumulative test scores. Gene expression profiling ordinal score (range, 0-39), threshold score (binary value=1 if ordinal score ≥34), and score variability were studied in multivariate Cox regression models to predict future clinical events. Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, gene expression profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were <0.001, 0.46, and 0.773, for gene expression profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4-2.3). The variability of a heart recipient's gene expression profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal gene-expression profiling test score.
    Transplantation 03/2014; 97(6):708-14. DOI:10.1097/01.TP.0000443897.29951.cf · 3.78 Impact Factor
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    ABSTRACT: To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR) and with cytomegalovirus (CMV) infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score>37% = AR) and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV) irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection.
    PLoS ONE 12/2013; 8(12):e82153. DOI:10.1371/journal.pone.0082153 · 3.53 Impact Factor
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    ABSTRACT: There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with posttransplant therapies that combine immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients) and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma. We observe marked virome compositional dynamics at the onset of the therapy and find that the total viral load increases with immunosuppression, whereas the bacterial component of the microbiome remains largely unaffected. The data provide insight into the relationship between the human virome, the state of the immune system, and the effects of pharmacological treatment and offer a potential application of the virome state to predict immunocompetence.
    Cell 11/2013; 155(5):1178-1187. DOI:10.1016/j.cell.2013.10.034 · 33.12 Impact Factor
  • Hannah Valantine, Christy I Sandborg
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    ABSTRACT: Central to the daily struggles that successful working women face is the misalignment of the current work culture and the values of the workforce. In addition to contributing to work-life integration conflicts, this disconnect perpetuates the gender leadership gap. The dearth of women at the highest ranks of academic medicine not only sends a clear message to women that they must choose between career advancement and their personal life but also represents a loss of talent for academic health centers as they fail to recruit and retain the best and the brightest. To close the gender leadership gap and to meet the needs of the next generation of physicians, scientists, and educators, the authors argue that the culture of academic medicine must change to one in which flexibility and work-life integration are core parts of the definition of success. Faculty must see flexibility policies, such as tenure clock extensions and parental leaves, as career advancing rather than career limiting. To achieve these goals, the authors describe the Stanford University School of Medicine Academic Biomedical Career Customization (ABCC) model. This framework includes individualized career plans, which span a faculty member's career, with options to flex up or down in research, patient care, administration, and teaching, and mentoring discussions, which ensure that faculty take full advantage of the existing policies designed to make career customization possible. The authors argue that with vision, determination, and focus, the academic medicine community can eliminate the gender leadership gap to achieve 50/50 by 2020.
    Academic medicine: journal of the Association of American Medical Colleges 08/2013; 88(10). DOI:10.1097/ACM.0b013e3182a34952 · 3.47 Impact Factor
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    ABSTRACT: We evaluated the potential effects of granulocyte colony-simulating factor (G- CSF) on the incidence of rejection and allograft vasculopathy in heart transplant recipients. Of 247 patients undergoing heart transplantation from 2000 to 2007, 52 (21%) developed leukopenia (white blood cell [WBC] <2.5 × 10(9)cells/L) in the absence of active infection, rejection, or malignancy. In 24 (46%) patients a clinical decision was made to treat the leukopenia with G-CSF (G-CSF group), and 28 (54%) Patients received no G-CSF (non-GCSF group). Patients followed up for 1 year after the period of leukopenia were assessed for allograft vasculopathy and acute rejection incidence. At baseline, the G-CSF group and the non-GCSF group did not differ in age, gender, race, heart failure etiology, creatinine, left ventricular ejection fraction (LVEF) or immunosupressive regimen. During 1-year follow-up there were no deaths in the G-CSF group, and 1 death in the non-GCSF group (P = .34). The incidence of rejection or progressive allograft vasculopathy was lower in the G-CSF group when compared with the non-GCSF group (2 [8%] vs 15 [53%]; P < .01). Multivariate analysis identified both prior rejection episodes and G-CSF therapy as factors associated with the combined end-point of rejection or progressive allograft vasculopathy (odds ratio [OR] = 7.89 [1.67-37.2] and OR = 0.09 [0.02-0.52], respectively). G-CSF therapy appears to be associated with a decreased incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients, suggesting a potential immunomodulatory effect of G-CSF.
    Transplantation Proceedings 07/2013; 45(6):2406-9. DOI:10.1016/j.transproceed.2013.01.106 · 0.95 Impact Factor
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    ABSTRACT: Purpose There is growing evidence that non-stenotic epicardial vasculopathy affects survival after heart transplantation. We have developed a model that estimates the risk of death due to vasculopathy by combining the ISHLT working formulation and the consensus statement of the German task force for cardiac allograft vasculopathy (CAV). Methods and Materials Coronary angiograms (n=996, 906 pts) performed at 30 days, 1 and 5 yrs post-transplant were evaluated according to the ISHLT (CAV0-CAV3) and the German task force (epicardial remodeling, peripheral obliteration) working formulations. Cox models were generated to estimate the risk of death, given these predictors. A combination model was designed to estimate vasculopathy-related risk of death at 10 yrs post-transplant. Results CAV0 was present in 85%, 78% and 45% of pts at 30 days, 1 year, and 5 years post-transplant; CAV1 was found in 14%, 17% and 36% of pts; CAV2 and CAV3 in 2%, 5% and 17% of pts; and remodeling was found in 10%, 18% and 45% of pts at 30 days, 1 and 5 yrs, respectively. Relative risks are presented in the table. Ten-year survival using the ISHLT classification showed sensitivity of 70%, specificity of 52% and a false classification rate of 48%. Ten-year survival as classified by epicardial remodeling showed sensitivity of 70%, specificity of 45% and a false classification rate of 43%. The combination of the ISHLT and German classification schemes had sensitivity of 88%, specificity of 29% and false classification rate of 39%. Conclusions A combination model incorporating the ISHLT working formulation and the presence of non-stenotic epicardial vasculopathy shows improved ability to identify pts at risk for death post-transplant and reduces false classification rates. View Within Article
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S27. DOI:10.1016/j.healun.2013.01.051 · 5.61 Impact Factor
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    ABSTRACT: The basis for increased mortality after heart transplant in non-Caucasians is poorly defined. We hypothesized that increased risk of adverse events is due to biological factors related to the alloimmune response. To test this hypothesis in the IMAGE study, we determined whether the event rate of the primary outcome (rejection with hemodynamic compromise, graft dysfunction, death, or retransplantation) varied by race in heart transplant recipients. We explored whether racial differences may be due to differences in levels of calcineurin inhibitors (CNI) or gene expression profile (GEP) scores.Methods and MaterialsWe studied the event rate of the primary outcome, comparing racial groups in the IMAGE population, stratified by time post-transplant. We assessed whether differences in event rate varied as a function of CNI levels and GEP score. Logistic regression was used to compute the relative risk across racial groups and linear modeling was used to measure the dependence of GEP score and CNI on race.ResultsWe found increased incidence of the primary endpoint in African Americans and other non-Caucasians, compared to Caucasians (18.3% and 22.2% vs. 8.5% respectively). African Americans had higher GEP score than Caucasians on CSA (p=0.01) despite similar levels. GEP score was higher, albeit tacrolimus blood level was lower, for other non-Caucasians than Caucasians.Conclusions Non-Caucasian heart transplant patients are 2.5-3 times more likely than Caucasians to experience rejection with hemodynamic compromise or death. Our data suggest that the increased risk of adverse outcomes may be due to the biology of the alloimmune response, which is less effectively abrogated by immunosuppression in non-Caucasians.GroupMonth post-txEvents/pt/yrTac median troughCSA median troughGEP score mean (Tac)GEP score mean (CSA)Caucasian7-120.098.816728.826.1 13-360.078.21443030.1 >360.057.01183030African American7-120.279.314130.532.2 13-360.188.412029.832.2 >360.147.111129.430.5Other non-Caucasian7-120.878.218329.728.5 13-360.217.017331.829.4 >360.075.712229.628.0
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S102-S103. DOI:10.1016/j.healun.2013.01.1022 · 5.61 Impact Factor
  • The Thoracic and Cardiovascular Surgeon 01/2013; 61(S 01). DOI:10.1055/s-0032-1332368 · 1.08 Impact Factor
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    ABSTRACT: The influence of donor-transmitted coronary atherosclerosis (DA) on plaque progression during the first year after cardiac transplantation (Tx) is unknown. Serial 3-dimensional intravascular ultrasound (IVUS) studies were performed within 8 weeks (baseline; BL) and at 1 year after Tx in 38 recipients. On the basis of maximum intimal thickness (MIT) at BL, recipients were divided into DA group (DA+; MIT≥0.5 mm, n=23) or non-DA group (DA-; MIT<0.5 mm, n=15). Plaque, lumen, and vessel volume indexes were calculated by volume/measured length (mm/mm) in the left anterior descending artery. Univariate and multivariate regression analyses were attempted to reveal clinical predictors of change in coronary dimensions. During the first year after Tx, plaque volume index increased significantly in DA+ group, but did not change in DA- Group (DA+, 3.0±1.5 to 4.1±1.5 mm/mm, P<0.0001: DA-, 1.2±0.4 to 1.3±0.5 mm/mm, P=0.53). In both groups vessel volume index decreased significantly (DA+, 16.3±3.6 to 14.6±3.3 mm/mm, P=0.003: DA-, 13.5±4.1 to 12.0±3.3 mm/mm, P=0.01), as did lumen volume index (DA+, 13.2±3.1 to 10.5±2.7 mm/mm, P<0.0001: DA-, 12.2±3.7 to 10.7±3.0 mm/mm, P=0.004). Univariate and multivariate regression analyses revealed that DA was one of the strongest predictors for plaque progression. DA was associated with significant plaque progression during the first year after Tx, and in conjunction with negative remodeling, may be an important determinant of cardiac allograft vasculopathy.
    Transplantation 06/2011; 91(12):1406-11. DOI:10.1097/TP.0b013e31821ab91b · 3.78 Impact Factor
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    ABSTRACT: Recent studies suggest that students' feelings of fit with a residency program substantially influence students' ranking of the program. As diversity issues become increasingly focal concerns, we investigate how perception of gender and racial diversity of a program influences students' rankings of the program. We focus on students pursuing surgical specialties and ask whether diversity concerns are more prominent among applicants to surgical programs than among applicants to nonsurgical programs. We invited all interviewees at all residency programs at the Stanford University School of Medicine to participate in our study in the spring of 2009. Nineteen residency programs, amounting to 1,657 residency interviewees, participated. Sixty-eight percent (n = 1,132) responded to the survey. Women and under-represented minority applicants differ in their assessments from male and non-under-represented minority applicants because women applying to surgical programs and under-represented minority students are less likely than others to perceive their prospective programs as diverse. However, perceived program diversity is an important factor that positively influences the program ranking decision for women and minorities pursuing surgical training. Surgical training programs that promote gender and racial diversity will likely be more successful in attracting women and minority students because women and minorities are especially sensitive to program diversity in both their perceptions and rankings of programs. Promoting women and minorities within programs and connecting women and minority applicants to outreach programs and mentors is pertinent to the recruitment of these traditionally under-represented groups to surgical programs.
    Journal of the American College of Surgeons 06/2011; 213(2):294-305. DOI:10.1016/j.jamcollsurg.2011.04.026 · 4.45 Impact Factor
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    ABSTRACT: Treatment of acute rejection (AR) in heart transplantation relies on histopathological grading of endomyocardial biopsies according to International Society for Heart and Lung Transplantation guidelines. Intragraft gene expression profiling may be a way to complement histological evaluation. Transcriptional profiling was performed on 26 endomyocardial biopsies, and expression patterns were compared with the 1990 International Society for Heart and Lung Transplantation AR grades. Importantly, transcriptional profiles from settings with an equivalent AR grade appeared the same. In addition, grade 0 profiles could not be distinguished from 1A profiles, and grade 3A profiles could not be distinguished from 3B profiles. Comparing the AR groupings (0+1A, 1B, and 3A+3B), 0+1A showed more striking differences from 1B than from 3A+3B. When these findings were extrapolated to the 2005 revised guidelines, the combination of 1A and 1B into a single category (1R) appears to have brought together endomyocardial biopsies with different underlying processes that are not evident from histological evaluation. Grade 1B was associated with upregulated immune response genes, as 1 categorical distinction from grade 1A. Although grade 1B was distinct from the clinically relevant AR grades 3A and 3B, all of these grades shared a small number of overlapping pathways consistent with common physiological underpinnings. The gene expression similarities and differences identified here in different AR settings have the potential to revise the clinical perspective on acute graft rejection, pending the results of larger studies.
    Circulation 05/2011; 123(20):2236-43. DOI:10.1161/CIRCULATIONAHA.109.913921 · 14.95 Impact Factor
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    ABSTRACT: Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs.
    Clinical Transplantation 05/2011; 25(5):E475-86. DOI:10.1111/j.1399-0012.2011.01476.x · 1.49 Impact Factor
  • K. K. Khush, J. Kubo, M. Desai, H. A. Valantine
    The Journal of Heart and Lung Transplantation 04/2011; 30(4). DOI:10.1016/j.healun.2011.01.192 · 5.61 Impact Factor
  • K. K. Khush, T. M. Snyder, S. R. Quake, H. A. Valantine
    The Journal of Heart and Lung Transplantation 04/2011; 30(4). DOI:10.1016/j.healun.2011.01.568 · 5.61 Impact Factor
  • The Journal of Heart and Lung Transplantation 04/2011; 30(4). DOI:10.1016/j.healun.2011.01.536 · 5.61 Impact Factor

Publication Stats

5k Citations
1,238.64 Total Impact Points

Institutions

  • 1991–2014
    • Stanford University
      • • Division of Cardiovascular Medicine
      • • Department of Pediatrics
      • • Falk Cardiovascular Research Center
      • • Department of Cardiothoracic Surgery
      Palo Alto, California, United States
  • 1987–2014
    • Stanford Medicine
      • • Falk Cardiovascular Research Center
      • • Division of Cardiovascular Medicine
      • • Department of Surgery
      • • Department of Medicine
      Stanford, California, United States
  • 2007
    • University of Bologna
      • Institute of Cardiology
      Bologna, Emilia-Romagna, Italy
    • Columbia University
      New York, New York, United States
  • 2002
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1998
    • University of California, Los Angeles
      Los Angeles, California, United States