Clinical Focus

  • Heart Transplantation
  • Cardiovascular Disease
  • Cardiology (Heart)

Academic Appointments

Professional Education

  • Fellowship:Stanford University School of Medicine (1976) CA
  • Residency:Stanford University School of Medicine (1976) CA
  • Medical Education:Stanford University School of Medicine (1972) CA
  • Internship:Stanford University School of Medicine (1973) CA
  • Board Certification: Advanced Heart Failure and Transplant Cardiology, American Board of Internal Medicine (2010)
  • Board Certification: Cardiovascular Disease, American Board of Internal Medicine (1979)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1977)
  • M.D., Stanford University, Cardiology Fellowship (1977)
  • M.D., Stanford University, Residency in Internal Medicine (1974)
  • M.D., Stanford University, Medicine (1972)


2013-14 Courses

Graduate and Fellowship Programs


Journal Articles

  • Granulocyte colony-stimulating factor therapy is associated with a reduced incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients. Transplantation proceedings Vrtovec, B., Haddad, F., Pham, M., Deuse, T., Fearon, W. F., Schrepfer, S., Leon, S., Vu, T., Valantine, H., Hunt, S. A. 2013; 45 (6): 2406-2409


    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.

    View details for DOI 10.1016/j.transproceed.2013.01.106

    View details for PubMedID 23953556

  • ST-Elevation Myocardial Infarction Following Heart Transplantation as an Unusual Presentation of Coronary Allograft Vasculopathy: A Case Report TRANSPLANTATION PROCEEDINGS Peter, S., HULME, O., Deuse, T., Vrtovec, B., Fearon, W. F., Hunt, S., Haddad, F. 2013; 45 (2): 787-791


    The presentation, mechanisms, and incidence of ST elevation myocardial infarction (STEMI) in heart transplant recipients have been characterized only to a limited degree in the current literature. Herein, we present a unique case of STEMI years after heart transplantation with a focus on the salient features of its diagnosis and interventions. We also provide a review of the epidemiology of this phenomenon.A 33-year-old woman who was status post cardiac transplantation for dilated cardiomyopathy presented to the clinic with mild nonspecific fatigue and concern after having noticed relative bradycardia compared with her posttransplantation baseline heart rate. Electrocardiogram (ECG) showed junctional rhythm and inferior ST elevations, likely reflecting nodal ischemia. Troponins were grossly positive and echocardiogram showed marked right ventricular dysfunction.Successful percutaneous coronary intervention (PCI) with aspiration thrombectomy and drug-eluting stent placement was emergently performed. The heart's rhythm soon returned to sinus tachycardia. Right ventricular wall-motion abnormalities resolved. The patient suffered no clinical sequelae of her STEMI.This case illustrated that "classic" symptoms of STEMI may not occur at all in the setting of heart transplantation. To our knowledge, this is the first case of posttransplantation STEMI presenting as asymptomatic bradycardia, and highlights the importance of maintaining high clinical suspicion for ischemia in transplant recipients with subtle changes. In reviewing the epidemiology of this case, we locate and bundle different types of studies that have directly or indirectly looked at STEMI in heart transplantation. For a variety of putative pathophysiological reasons, STEMI is indeed a rare manifestation of the common transplant phenomenon of coronary artery vasculopathy (CAV).

    View details for DOI 10.1016/j.transproceed.2012.08.021

    View details for Web of Science ID 000316772500055

    View details for PubMedID 23498821

  • Clinical and Functional Correlates of Early Microvascular Dysfunction After Heart Transplantation CIRCULATION-HEART FAILURE Haddad, F., Khazanie, P., Deuse, T., Weisshaar, D., Zhou, J., Nam, C. W., Vu, T. A., Gomari, F. A., Skhiri, M., Simos, A., Schnittger, I., Vrotvec, B., Hunt, S. A., Fearon, W. F. 2012; 5 (6): 759-768


    Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine the risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients.Sixty-three heart transplant recipients who had coronary physiology assessment, right heart catheterization, and echocardiography performed at the time of their first annual evaluation were included in the study. Microvascular dysfunction was assessed using the recently described index of microcirculatory resistance. The presence of microvascular dysfunction, predefined by an index of microcirculatory resistance >20, was observed in 46% of patients at 1 year. A history of acute rejection and undersized donor hearts were associated with microvascular dysfunction at 1 year, with odds ratio of 4.0 (1.3-12.8) and 3.6 (1.2-11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1±0.7 versus 3.5±0.7 L/min per m(2); P=0.02) and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices ([0.54±0.09 versus 0.43±0.09; P<0.01] and [0.47±0.14 versus 0.32±0.05; P<0.01], respectively). Microvascular dysfunction was also associated with a higher likelihood of death, graft failure, or allograft vasculopathy at 5 years after transplant (hazard ratio, 2.52 [95% CI, 1.04-5.91]).A history of acute rejection during the first year and smaller donor hearts were identified as risk factors for early microvascular dysfunction. Microvascular dysfunction assessed using index of microcirculatory resistances at 1 year was also associated with worse graft function and possibly worse clinical outcomes.

    View details for DOI 10.1161/CIRCHEARTFAILURE.111.962787

    View details for Web of Science ID 000313580100023

    View details for PubMedID 22933526

  • Heart transplant recipient selection issues: Limited assets, infinite possibilities JOURNAL OF HEART AND LUNG TRANSPLANTATION Hunt, S. A. 2012; 31 (7): 675-676

    View details for DOI 10.1016/j.healun.2012.04.001

    View details for Web of Science ID 000305544700001

    View details for PubMedID 22576058

  • Comparison of Drug-Eluting Versus Bare Metal Stents in Cardiac Allograft Vasculopathy AMERICAN JOURNAL OF CARDIOLOGY Tremmel, J. A., Ng, M. K., Ikeno, F., Hunt, S. A., Lee, D. P., Yeung, A. C., Fearon, W. F. 2011; 108 (5): 665-668


    Although not a definitive treatment, percutaneous coronary intervention offers a palliative benefit to patients with cardiac allograft vasculopathy. Given the superior outcomes with drug-eluting stents (DESs) over bare metal stents (BMSs) in native coronary artery disease, similar improvements might be expected in transplant patients; however, the results have been mixed. Consecutive cardiac transplantation recipients at a single center receiving a stent for de novo cardiac allograft vasculopathy from 1997 to 2009 were retrospectively analyzed according to receipt of a DES versus a BMS. The angiographic and clinical outcomes were subsequently evaluated at 1 year. The baseline clinical and procedural characteristics were similar among those receiving DESs (n = 18) and BMSs (n = 16). Quantitative coronary angiography revealed no difference in the reference diameter, lesion length, or pre-/postprocedural minimal luminal diameter. At the 12-month angiographic follow-up visit, the mean lumen loss was significantly lower in the DES group than in the BMS group (0.19 ± 0.73 mm vs 0.76 ± 0.97 mm, p = 0.02). The DES group also had a lower rate of in-stent restenosis (12.5% vs 33%, p = 0.18), as well as a significantly lower rate of target lesion revascularization (0% vs 19%, p = 0.03). At 1 year, DESs were associated with a lower composite rate of cardiac death and nonfatal myocardial infarction (12% vs 38%, p = 0.04). In conclusion, DESs are safe and effective in the suppression of neointimal hyperplasia after percutaneous coronary intervention for cardiac allograft vasculopathy, resulting in significantly lower rates of late lumen loss and target lesion revascularization, as well as a reduced combined rate of cardiac death and nonfatal myocardial infarction.

    View details for DOI 10.1016/j.amjcard.2011.04.014

    View details for Web of Science ID 000294751000009

    View details for PubMedID 21684511

  • Behcet's disease and heart transplantation: A word of caution JOURNAL OF HEART AND LUNG TRANSPLANTATION Hollander, S. A., Yasnovsky, J. R., Reinhartz, O., Chan, F., Sandborg, C., Hunt, S., Bernstein, D., Chin, C. 2010; 29 (11): 1306-1308


    Behcet's disease is a rare autoimmune disease characterized by oral and genital ulcers, and by multisystem disease, including arthritis, neurologic complications and vasculitis. Large-vessel and coronary artery aneurysms are often an indication for surgery, but the return of aneurysms, thrombosis, and the tendency to exhibit an exaggerated inflammatory response at puncture sites (pathergy) complicate surgical recovery. As such, cardiac transplantation, which requires atrial and large-vessel anastomoses, has not been reported in patients with Behcet's disease. We report the first orthotopic heart transplant with >1-year survival in a patient with Behcet's disease despite major complications. The investigators remain pessimistic about cardiac transplantation in patients with Behcet's disease until advances in preventing recurrent vascular pathology ensue.

    View details for DOI 10.1016/j.healun.2010.07.010

    View details for Web of Science ID 000284030700015

    View details for PubMedID 20822920

  • Evidence-Based Management of Right Heart Failure: a Systematic Review of an Empiric Field REVISTA ESPANOLA DE CARDIOLOGIA Skhiri, M., Hunt, S. A., Denault, A. Y., Haddad, F. 2010; 63 (4): 451-471


    In recent years, several studies have shown that right ventricular function is an important predictor of survival in patients with congenital heart disease, pulmonary hypertension or left heart failure. Our understanding of right heart failure has improved considerably over the last two decades. In this review article, our objective was to provide a critical summary of the evidence underlying the management of right heart failure. A systematic review of the literature was performed using PubMed and the latest issue of the Cochrane Central Register of Controlled Trials to identify studies conducted between January 1975 and January 2010. The literature search encompassed observational studies, randomized controlled trials and meta-analyses. The evidence underlying the use of beta-blockade, angiotensin-converting enzyme inhibitors, inhaled nitric oxide, hydralazine, warfarin, and resynchronization therapy in right heart failure was systematically reviewed. Emerging new therapies, such as metabolic modulators, and the pearls and pitfalls of managing right heart failure are also discussed in the article.

    View details for Web of Science ID 000276217300011

    View details for PubMedID 20334811

  • Changing trends in infectious disease in heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Deuse, T., Pham, M., Khazanie, P., Rosso, F., Luikart, H., Valantine, H., Leon, S., Vu, T. A., Hunt, S. A., Oyer, P., Montoya, J. G. 2010; 29 (3): 306-315


    During the past 25 years, advances in immunosuppression and the use of selective anti-microbial prophylaxis have progressively reduced the risk of infection after heart transplantation. This study presents a historical perspective of the changing trends of infectious disease after heart transplantation.Infectious complications in 4 representative eras of immunosuppression and anti-microbial prophylaxis were analyzed: (1) 38 in the pre-cyclosporine era (1978-1980), (2) 72 in the early cyclosporine era (1982-1984), where maintenance immunosuppression included high-dose cyclosporine and corticosteroid therapy; (3) 395 in the cyclosporine era (1988-1997), where maintenance immunosuppression included cyclosporine, azathioprine, and lower corticosteroid doses; and (4) 167 in the more recent era (2002-2005), where maintenance immunosuppression included cyclosporine and mycophenolate mofetil.The overall incidence of infections decreased in the 4 cohorts from 3.35 episodes/patient to 2.03, 1.35, and 0.60 in the more recent cohorts (p < 0.001). Gram-positive bacteria are emerging as the predominant cause of bacterial infections (28.6%, 31.4%, 51.0%, 67.6%, p = 0.001). Cytomegalovirus infections have significantly decreased in incidence and occur later after transplantation (88 +/- 77 days, pre-cyclosporine era; 304 +/- 238 days, recent cohort; p < 0.001). Fungal infections also decreased, from an incidence of 0.29/patient in the pre-cyclosporine era to 0.08 in the most recent era. A major decrease in Pneumocystis jiroveci and Nocardia infections has also occurred.The overall incidence and mortality associated with infections continues to decrease in heart transplantation and coincides with advances in immunosuppression, the use of selective anti-microbial prophylaxis, and more effective treatment regimens.

    View details for DOI 10.1016/j.healun.2009.08.018

    View details for Web of Science ID 000276005200013

    View details for PubMedID 19853478

  • The Efficacy of Implantable Cardioverter-Defibrillators in Heart Transplant Recipients Results From a Multicenter Registry CIRCULATION-HEART FAILURE Tsai, V. W., Cooper, J., Garan, H., Natale, A., Ptaszek, L. M., Ellinor, P. T., Hickey, K., Downey, R., Zei, P., Hsia, H., Wang, P., Hunt, S., Haddad, F., Al-Ahmad, A. 2009; 2 (3): 197-201


    Sudden cardiac death among orthotopic heart transplant recipients is an important mechanism of death after cardiac transplantation. The role for implantable cardioverter-defibrillators (ICDs) in this population is not well established. This study sought to determine whether ICDs are effective in preventing sudden cardiac death in high-risk heart transplant recipients.We retrospectively analyzed the records of all orthotopic heart transplant patients who had ICD implantation between January 1995 and December 2005 at 5 heart transplant centers. Thirty-six patients were considered high risk for sudden cardiac death. The mean age at orthotopic heart transplant was 44+/-14 years, the majority being male (n=29). The mean age at ICD implantation was 52+/-14 years, whereas the average time from orthotopic heart transplant to ICD implant was 8 years +/-6 years. The main indications for ICD implantation were severe allograft vasculopathy (n=12), unexplained syncope (n=9), history of cardiac arrest (n=8), and severe left ventricular dysfunction (n=7). Twenty-two shocks were delivered to 10 patients (28%), of whom 8 (80%) received 12 appropriate shocks for either rapid ventricular tachycardia or ventricular fibrillation. The shocks were effective in terminating the ventricular arrhythmias in all cases. Three (8%) patients received 10 inappropriate shocks. Underlying allograft vasculopathy was present in 100% (8 of 8) of patients who received appropriate ICD therapy.Use of ICDs after heart transplantation may be appropriate in selected high-risk patients. Further studies are needed to establish an appropriate prevention strategy in this population.

    View details for DOI 10.1161/CIRCHEARTFAILURE.108.814525

    View details for Web of Science ID 000269161600007

    View details for PubMedID 19808340

  • Right Ventricular Dysfunction Predicts Poor Outcome Following Hemodynamically Compromising Rejection JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Fisher, P., Pham, M., Berry, G., Weisshaar, D., Kuppahally, S., Vrtovec, B., Deuse, T., Virani, S., Fearon, W., Valantine, H., Hunt, S. 2009; 28 (4): 312-319


    Hemodynamically compromising rejection (HCR) is a major cause of mortality and morbidity after heart transplantation. Right ventricular (RV) function is a strong predictor of outcome in patients with heart failure and myocarditis. The objective of the current study is to determine whether RV dysfunction predicts event-free survival in patients with HCR.Medical records of 548 heart transplant patients followed at Stanford University between January 1998 and January 2007 were reviewed. HCR was defined as a rejection episode requiring hospitalization for heart failure. Univariate and multivariate analyses were performed to identify risk factors for death or retransplantation at 1 year.HCR occurred in 71 patients (12.9%). Death or retransplantation at 1 year occurred in 28 patients (39%). Univariate analysis identified non-cellular rejection (odds ratio [OR] = 3.20, p = 0.021), the need for inotropic support (OR = 4.80, p = 0.007), RV dysfunction (OR = 4.63, p = 0.006), left ventricular ejection fraction (OR = 0.941, p = 0.031) and acute renal failure (OR = 3.82, p = 0.010) as predictors of death or retransplantation at 1 year. Multivariate analysis identified RV dysfunction (OR = 4.80, p = 0.007) and the need for inotropic support (OR = 5.00, p = 0.009) as predictors of death or retransplantation at 1 year.In the modern era of immunosuppression, HCR remains a major complication after heart transplantation. RV dysfunction was identified as a novel risk factor for death or retransplantation following HCR.

    View details for DOI 10.1016/j.healun.2008.12.023

    View details for Web of Science ID 000265042300003

    View details for PubMedID 19332256

  • Twenty-year survivors of heart transplantation at Stanford University AMERICAN JOURNAL OF TRANSPLANTATION Deuse, T., Haddad, F., Pham, M., Hunt, S., Valantine, H., BATES, M. J., Mallidi, H. R., Oyer, P. E., Robbins, R. C., Reitz, B. A. 2008; 8 (9): 1769-1774


    Human heart transplantation started 40 years ago. Medical records of all cardiac transplants performed at Stanford were reviewed. A total of 1446 heart transplantations have been performed between January 1968 and December 2007 with an increase of 1-year survival from 43.1% to 90.2%. Sixty patients who were transplanted between 1968 and 1987 were identified who survived at least 20 years. Twenty-year survivors had a mean age at transplant of 29.4 +/- 13.6 years. Rejection-free and infection-free 1-year survivals were 14.3% and 18.8%, respectively. At their last follow-up, 86.7% of long-term survivors were treated for hypertension, 28.3% showed chronic renal dysfunction, 6.7% required hemodialysis, 10% were status postkidney transplantation, 13.3% were treated for diabetes mellitus, 36.7% had a history of malignancy and 43.3% had evidence of allograft vasculopathy. The half-life conditional on survival to 20 years was 28.1 years. Eleven patients received a second heart transplant after 11.9 +/- 8.0 years. The most common causes of death were allograft vasculopathy (56.3%) and nonlymphoid malignancy (25.0%). Twenty-year survival was achieved in 12.5% of patients transplanted before 1988. Although still associated with considerable morbidity, long-term survival is expected to occur at much higher rates in the future due to major advances in the field over the past decade.

    View details for DOI 10.1111/j.1600-6143.2008.02310.x

    View details for Web of Science ID 000258401700004

    View details for PubMedID 18557718

  • The changing face of heart transplantation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Hunt, S. A., Haddad, F. 2008; 52 (8): 587-598


    It has been 40 years since the first human-to-human heart transplant performed in South Africa by Christiaan Barnard in December 1967. This achievement did not come as a surprise to the medical community but was the result of many years of early pioneering experimental work by Alexis Carrel, Frank Mann, Norman Shumway, and Richard Lower. Since then, refinement of donor and recipient selection methods, better donor heart management, and advances in immunosuppression have significantly improved survival. In this article, we hope to give a perspective on the changing face of heart transplantation. Topics that will be covered in this review include the changing patient population as well as recent advances in transplantation immunology, organ preservation, allograft vasculopathy, and immune tolerance.

    View details for DOI 10.1016/j.jacc.2008.05.020

    View details for Web of Science ID 000258394000001

    View details for PubMedID 18702960

  • Effect of rapamycin therapy on coronary artery physiology early after cardiac transplantation AMERICAN HEART JOURNAL Sinha, S. S., Pham, M. X., Vagelos, R. H., Perlroth, M. G., Hunt, S. A., Lee, D. P., Valantine, H. A., Yeung, A. C., Fearon, W. F. 2008; 155 (5)


    Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown.Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18).At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 +/- 0.06 to 0.82 +/- 0.06, P = .009) but did not change in the rapamycin group (0.91 +/- 0.05 to 0.89 +/- 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 +/- 1.7 to 3.2 +/- 1.0, P = .76; and 27.5 +/- 18.1 to 19.1 +/- 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 +/- 0.8 to 3.8 +/- 1.4, P < .03; and 27.0 +/- 11.5 to 17.6 +/- 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation.Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.

    View details for DOI 10.1016/j.ahj.2008.02.004

    View details for Web of Science ID 000256001500014

    View details for PubMedID 18440337

  • Right ventricular function in cardiovascular disease, Part II - Pathophysiology, clinical importance, and management of right ventricular failure CIRCULATION Haddad, F., Doyle, R., Murphy, D. J., Hunt, S. A. 2008; 117 (13): 1717-1731
  • Right ventricular function in cardiovascular disease, part I - Anatomy, physiology, aging, and functional assessment of the right ventricle CIRCULATION Haddad, F., Hunt, S. A., Rosenthal, D. N., Murphy, D. J. 2008; 117 (11): 1436-1448
  • Reversibility of trastuzumab cardiotoxicity: Is the concept alive and well? Reply JOURNAL OF CLINICAL ONCOLOGY Telli, M. L., Carlson, R. W., Guardino, A. E., Hunt, S. A., Witteles, R. M. 2007; 25 (34): 5533-5534
  • Outcome in cardiac recipients of donor hearts with increased left ventricular wall thickness AMERICAN JOURNAL OF TRANSPLANTATION Kuppahally, S. S., Valantine, H. A., Weisshaar, D., Parekh, H., Hung, Y. Y., Haddad, F., Fowler, M., Vagelos, R., Perlroth, M. G., Robbins, R. C., Hunt, S. A. 2007; 7 (10): 2388-2395


    The ongoing shortage of donors for cardiac transplantation has led to a trend toward acceptance of donor hearts with some structural abnormalities including left ventricular hypertrophy. To evaluate the outcome in recipients of donor hearts with increased left ventricular wall thickness (LVWT), we retrospectively analyzed data for 157 cardiac donors and respective recipients from January 2001 to December 2004. There were 47 recipients of donor heart with increased LVWT >or=1.2 cm, which constituted the study group and 110 recipients of a donor heart with normal LVWT < 1.2 cm that formed the control group. At 3 +/- 1.5 years, recipient survival was lower (50% vs. 82%, p = 0.0053) and incidence of allograft vasculopathy was higher (50% vs. 22%, p = 0.05) in recipients of donor heart with LVWT > 1.4 cm as compared to LVWT 1.4 cm (p = 0.003), recipient preoperative ventricular assist device (VAD) support (p = 0.04) and bypass time > 150 min (p = 0.05) were predictors of reduced survival. Our results suggest careful consideration of donor hearts with echocardiographic evidence of increased LVWT in the absence of hypovolemia, because they may be associated with poorer outcomes; such hearts should potentially be reserved only for the most desperately ill recipients.

    View details for DOI 10.1111/j.1600-6143.2007.01930.x

    View details for Web of Science ID 000249167000022

    View details for PubMedID 17845572

  • Trastuzumab-related cardiotoxicity: Calling into question the concept of reversibility JOURNAL OF CLINICAL ONCOLOGY Telli, M. L., Hunt, S. A., Carlson, R. W., Guardino, A. E. 2007; 25 (23): 3525-3533


    To assess the spectrum and reversibility of the cardiotoxicity observed in the adjuvant trastuzumab trials.The design and efficacy of the major adjuvant trastuzumab trials was assessed, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group N9831, Herceptin Adjuvant, Breast Cancer International Research Group 006, and Finland Herceptin trials. The cardiotoxicity data were evaluated with a focus on the follow-up cardiac evaluations of women who were diagnosed with cardiotoxicity. Proposed mechanisms of trastuzumab-related cardiotoxicity were considered. The natural history of congestive heart failure (CHF) was reviewed with the goal of placing the trastuzumab experience in context.Up to 4% of patients enrolled onto the adjuvant trastuzumab trials experienced severe CHF during treatment. In these trials, early stopping rules that identified an unacceptable level of cardiotoxicity were never reached. Despite this, a large number of patients on these trials experienced some form of cardiotoxicity that ultimately required discontinuation of trastuzumab. Approximately 14% of patients in the NSABP B-31 trial discontinued trastuzumab because of asymptomatic decreases in left ventricular ejection fraction (LVEF). Results of follow-up cardiac evaluations of patients diagnosed with any degree of cardiotoxicity in the NSABP B-31 trial document that a clinically significant proportion of patients have sustained decrements in their LVEF to less than 50%.Adjuvant trastuzumab provides substantial benefits to patients with human epidermal growth factor receptor 2-positive breast cancer, however, competing immediate and long-term cardiovascular risks are a great concern. Continued cardiac follow-up of these women is of critical importance.

    View details for DOI 10.1200/JCO.2007.11.0106

    View details for Web of Science ID 000248744300023

    View details for PubMedID 17687157

  • Changes in coronary anatomy and physiology after heart transplantation AMERICAN JOURNAL OF CARDIOLOGY Hirohata, A., Nakamura, M., Waseda, K., Honda, Y., Lee, D. P., Vagelos, R. H., Hunt, S. A., Valantine, H. A., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Fearon, W. F. 2007; 99 (11): 1603-1607


    Cardiac allograft vasculopathy (CAV) is a progressive process involving the epicardial and microvascular coronary systems. The timing of the development of abnormalities in these 2 compartments and the correlation between changes in physiology and anatomy are undefined. The invasive evaluation of coronary artery anatomy and physiology with intravascular ultrasound, fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance (IMR) was performed in the left anterior descending coronary artery during 151 angiographic evaluations of asymptomatic heart transplant recipients from 0 to >5 years after heart transplantation (HT). There was no angiographic evidence of significant CAV, but during the first year after HT, fractional flow reserve decreased significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7% to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3 vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the microvasculature. As the IMR increased, fractional flow reserve increased (0.86 +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to those with IMRs > or =40), despite no difference in percentage plaque volume (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT, anatomic and physiologic evidence of epicardial CAV was found. Later after HT, the physiologic effect of epicardial CAV may be less, because of increased microvascular dysfunction.

    View details for DOI 10.1016/j.amjcard.2007.01.039

    View details for Web of Science ID 000247121700024

    View details for PubMedID 17531589

  • Interplay between systemic inflammation and markers of insulin resistance in cardiovascular prognosis after heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Biadi, O., Potena, L., Fearon, W. F., Luikart, H. I., Yeung, A., Ferrara, R., Hunt, S. A., Mocarski, E. S., Valantine, H. A. 2007; 26 (4): 324-330


    Metabolic and immuno-inflammatory risk factors contribute to cardiac allograft vasculopathy (CAV) pathogenesis. Although systemic inflammation, as detected by C-reactive protein (CRP), predicts CAV development, the relationship between CRP and markers of metabolic abnormalities remains unexplored.CRP and the entire metabolic panel were evaluated in 98 consecutive heart transplant recipients at the time of annual coronary angiography, 5.8 years after transplant (range, 1-12 years). A ratio of triglycerides (TG) to high-density lipoproteins (HDL) of 3.0 or more was considered a marker of insulin resistance. CAV prevalence was defined by angiography, and subsequent prognosis was evaluated as incidence of major cardiac adverse events.CRP was higher in the 34 patients with angiographic CAV than in those without CAV (1.10 +/- 0.20 vs 0.50 +/- 0.05 mg/dl, p < 0.001). Patients with insulin resistance had higher CRP concentrations (p = 0.023) and higher CAV prevalence (p = 0.005). High CRP and a TG/HDL of 3.0 or more were independently associated with an increased likelihood of CAV (odds ratio, > or = 3.9; p = 0.02) and predicted an increased risk of major cardiac adverse events. The combination of high CRP and a TG/HDL of 3.0 or more identified a subgroup of patients having a 4-fold increased risk for CAV and a 3-fold increased risk for major cardiac adverse events compared with patients with low CRP and normal values for metabolic indicators.Both CRP and insulin resistance, as estimated by TG/HDL, appear to be strong, synergic risk factors for CAV and for major cardiac adverse events. These findings support the hypothesis that in heart transplant recipients, systemic inflammation may be an important mediator of graft vascular injury associated with metabolic syndrome.

    View details for DOI 10.1016/j.healun.2007.01.020

    View details for Web of Science ID 000245725100004

    View details for PubMedID 17403472

  • Pulmonary nocardiosis in a heart transplant patient: Case report and review of the literature JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Hunt, S. A., Perlroth, M., Valantine, H., Doyle, R., Montoya, J. 2007; 26 (1): 93-97


    Pulmonary infection with Nocardia is an uncommon but serious infection found in immunocompromised patients. We describe a rapidly progressive pulmonary nocardiosis in a heart transplant patient. We then review the common clinical features of Nocardia infection in transplant recipients, outlining the challenges in its diagnosis and management. We also review the differences between Pneumocystis jiroveci prophylaxis regimens with respect to concomitant prophylaxis of Nocardia and other opportunistic infections.

    View details for DOI 10.1016/j.healun.2006.11.002

    View details for Web of Science ID 000243950900015

    View details for PubMedID 17234524

  • Giant coronary aneurysms in heart transplantation: an unusual presentation of cardiac allograft vasculopathy JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Perez, M., Fleischmann, D., Valantine, H., Hunt, S. A. 2006; 25 (11): 1367-1370


    Cardiac allograft vasculopathy is a leading cause of death during long-term follow-up of heart transplant recipients. We report 2 cases of cardiac allograft vasculopathy associated with giant coronary aneurysms. To our knowledge, these are the first reported cases of spontaneous giant coronary aneurysms in heart transplant recipients.

    View details for DOI 10.1016/j.healun.2006.07.006

    View details for Web of Science ID 000242222100015

    View details for PubMedID 17097503

  • Taking heart - Cardiac transplantation past, present, and future NEW ENGLAND JOURNAL OF MEDICINE Hunt, S. A. 2006; 355 (3): 231-235

    View details for Web of Science ID 000239097600002

    View details for PubMedID 16855261

  • Discordant changes in epicardial and microvascular coronary physiology after cardiac transplantation: Physiologic investigation for transplant arteriopathy II (PITA II) study JOURNAL OF HEART AND LUNG TRANSPLANTATION Fearon, W. F., Hirohata, A., Nakamura, M., Luikart, H., Lee, D. P., Vagelos, R. H., Hunt, S. A., Valantine, H. A., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2006; 25 (7): 765-771


    Investigating changes in coronary physiology that occur after cardiac transplantation has been challenging. Simultaneous and independent assessment of the epicardial artery by measuring fractional flow reserve (FFR) and of the microvasculature by calculating the index of microvascular resistance (IMR) with a single coronary pressure wire may be useful.Twenty-five asymptomatic patients with normal coronary angiograms underwent FFR, thermodilution-derived IMR and coronary flow reserve (CFR) and intravascular ultrasound (IVUS) evaluation soon after cardiac transplantation and 1 year later.FFR significantly worsened (0.90 +/- 0.05 at baseline to 0.85 +/- 0.06 at 1 year, p = 0.004). FFR correlated strongly with percent plaque volume as measured by IVUS (r = -0.58, p < 0.0001). IMR improved significantly (29.2 +/- 15.9 at baseline to 19.3 +/- 7.6 units at 1 year, p = 0.007). CFR increased, but not significantly (2.6 +/- 1.4 at baseline to 3.2 +/- 1.2 at 1 year, p = not significant). Diabetes and donor heart ischemic time independently predicted baseline IMR. Treatment with rapamycin independently predicted FFR at 1 year.New coronary physiologic measures, FFR and IMR, show that epicardial artery physiology worsens and correlates with anatomic changes, whereas microvascular physiology improves during the first year after cardiac transplantation. CFR, the traditional method for evaluating coronary circulatory physiology, did not identify these changes.

    View details for DOI 10.1016/j.healun.2006.03.003

    View details for Web of Science ID 000239019700003

    View details for PubMedID 16818118

  • Wound healing complications with de novo sirolimus versus mycophenolate mofetil-based regimen in cardiac transplant recipients AMERICAN JOURNAL OF TRANSPLANTATION Kuppahally, S., Al-Khaldi, A., Weisshaar, D., Valantine, H. A., Oyer, P., Robbins, R. C., Hunt, S. A. 2006; 6 (5): 986-992


    Sirolimus was introduced in de novo immunosuppression at Stanford University in view of its favorable effects on reduced rejection and cardiac allograft vasculopathy. After an apparent increase in the incidence of post-surgical wound complications as well as symptomatic pleural and pericardial effusions, we reverted to a mycophenolate mofetil (MMF)-based regimen. This retrospective study compared the outcome in heart transplant recipients on sirolimus (48 patients) with those on MMF (46 patients) in de novo immunosuppressive regimen. The incidence of any post-surgical wound complication (52% vs. 28%, p=0.019) and deep surgical wound complication (35% vs. 13%, p=0.012) was significantly higher in patients on sirolimus than on MMF. More patients on sirolimus also had symptomatic pleural (p=0.035) and large pericardial effusions (p=0.033) requiring intervention. Logistic regression analysis showed sirolimus (p=0.027) and longer cardiac bypass time (OR=1.011; p=0.048) as risk factors for any wound complication. Sirolimus in de novo immunosuppression after cardiac transplantation was associated with a significant increase in the incidence of post-surgical wound healing complications as well as symptomatic pleural and pericardial effusions.

    View details for DOI 10.1111/j.1600-6143.2006.01282.x

    View details for Web of Science ID 000236860700015

    View details for PubMedID 16611334

  • Recurrence of iron deposition in the cardiac allograft in a patient with non-HFE hemochromatosis JOURNAL OF HEART AND LUNG TRANSPLANTATION Kuppahally, S. S., Hunt, S. A., Valantine, H. A., Berry, G. J. 2006; 25 (1): 144-147


    We report the case of a 36-year-old woman with a diagnosis of idiopathic dilated cardiomyopathy who underwent cardiac transplantation. The results of her initial iron studies were normal, but hemochromatosis was suspected after microscopy of the explanted heart revealed iron deposition. By 6 months post-transplantation, iron deposition was detected in her surveillance endomyocardial biopsy specimens and studies then confirmed the existence of non-HFE hemochromatosis. The patient has been stable on treatment with regular phlebotomies and a low vitamin C diet.

    View details for DOI 10.1016/j.healun.2005.08.002

    View details for Web of Science ID 000234610200025

    View details for PubMedID 16399547

  • Use of the implantable cardioverter-defibrillator in long-term survivors of orthotopic heart transplantation HEART RHYTHM Ptaszek, L. M., Wang, P. J., Hunt, S. A., Valantine, H., Perlroth, M., Al-Ahmad, A. 2005; 2 (9): 931-933


    Orthotopic heart transplantation is considered an effective treatment for patients with refractory heart failure. The long-term survival of orthotopic heart transplantation recipients has increased over the last several decades, but many long-term survivors of orthotopic heart transplantation develop graft atherosclerosis and associated left ventricular dysfunction. The risk of sudden cardiac death in long-term survivors of orthotopic heart transplantation with these complications is believed to be high. There are no data on the usefulness of implantable cardioverter-defibrillators (ICDs) in this population; therefore, we report our early experience with ICD placement in such patients.The purpose of this study was to examine the use of ICDs in adults who are long-term survivors of heart transplantation.We retrospectively reviewed all adult patients who underwent orthotopic heart transplantation at Stanford University Hospital (Stanford, CA, USA) from 1980 to 2004. All patients who received an ICD after transplant were included in this study. We reviewed demographic data, medical history, ejection fraction, presence of graft atherosclerosis, indication for ICD placement, and any device therapy delivered.Of the 925 patients who had orthotopic heart transplantation during this time period, 493 patients were alive at the beginning of the year 2000. Of these patients, 10 ( approximately 2%) had subsequent placement of an ICD. All 10 patients were male. The average age at orthotopic heart transplantation was 37.8 years. The average age at ICD placement was 50.5 years. The average time from orthotopic heart transplantation to ICD placement was 14.6 years. The average ejection fraction at the time of implant was 46.5%. Five of the 10 patients had a low ejection fraction (within this subgroup, the average ejection fraction was 31%, range 15%-45%) and graft atherosclerosis. ICDs were placed because of symptomatic episodes of ventricular tachycardia (3 patients), low ejection fraction and severe graft atherosclerosis without symptoms (3 patients), and after thorough evaluation for otherwise unexplained syncope (4 patients). The average follow-up after device implantation was 13 months. Complications related to ICD placement were an infected ICD system requiring explant in one patient and a lead fracture in another patient. Three patients had subsequent appropriate shocks for ventricular arrhythmias, and one patient underwent a second orthotopic heart transplantation. One patient died of malignancy.Use of the ICD in long-term survivors of orthotopic heart transplantation should be considered in appropriately selected patients. Further data are needed regarding ICD use in this population.

    View details for DOI 10.1016/j.hrthm.2005.06.018

    View details for Web of Science ID 000231986200008

    View details for PubMedID 16171746

  • Glucose intolerance, as reflected by hemoglobin A(1c) level, is associated with the incidence and severity of transplant coronary artery disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kato, T., Chan, M. C., Gao, S. Z., Schroeder, J. S., Yokota, M., Murohara, T., Iwase, M., Noda, A., Hunt, S. A., Valantine, H. A. 2004; 43 (6): 1034-1041


    The possible effect of plasma hemoglobin A(1c) (HbA(1c)) on the development of transplant coronary artery disease (TxCAD) was investigated.Glucose intolerance is implicated as a risk factor for TxCAD. However, a relationship between HbA(1c) and TxCAD has not been demonstrated.Plasma HbA(1c) was measured in 151 adult patients undergoing routine annual coronary angiography at a mean period of 4.1 years after heart transplantation. Intracoronary ultrasound (ICUS) was also performed in 42 patients. Transplant CAD was graded by angiography as none, mild (stenosis in any vessel < or =30%), moderate (31% to 69%), or severe (> or =70%) and was defined by ICUS as a mean intimal thickness (MIT) > or =0.3 mm in any coronary artery segment. The association between TxCAD and established risk factors was examined.Plasma HbA(1c) increased with the angiographic grade of TxCAD (5.6%, 5.8%, 6.4%, and 6.2% for none, mild, moderate, and severe disease, respectively; p < 0.05 for none vs. moderate or severe) and correlated with disease severity (r = 0.24, p < 0.05). The HbA(1c) level was higher in patients with MIT > or =0.3 mm than in those with MIT <0.3 mm (6.4% vs. 5.7%, p < 0.05). Multivariate logistic regression analysis identified HbA(1c) as an independent predictor of TxCAD, as detected by angiography or ICUS (odds ratios 1.9 and 2.4, 95% confidence intervals 1.5 to 6.3 [p = 0.010] and 1.3 to 4.2 [p < 0.005], respectively).Persistent glucose intolerance, as reflected by plasma HbA(1c), is associated with the occurrence of TxCAD and may play an important role in its pathogenesis.

    View details for DOI 10.1016/j.jacc.2003.08.063

    View details for Web of Science ID 000220212400018

    View details for PubMedID 15028363

  • Cardiac xenotransplantation CORONARY ARTERY DISEASE Pham, M. X., Hunt, S. A., Johnson, F. L. 2004; 15 (2): 99-105
  • Analysis of survivors more than 10 years after heart transplantation in the cyclosporine era: Stanford experience JOURNAL OF HEART AND LUNG TRANSPLANTATION Shiba, N., Chan, M. C., Kwok, B. W., Valantine, H. A., Robbins, R. C., Hunt, S. A. 2004; 23 (2): 155-164


    Truly long term survival post heart transplantation has become increasingly frequent over the past two decades.We analyzed multiple clinical outcomes in the cohort of 140 patients in the Stanford database who underwent heart transplantation after the introduction of cyclosporine-based immunosuppression in 1980 and survived >10 years after transplantation.We found generally excellent functional status in these patients, but a high incidence of hypertension, renal dysfunction, and graft CAD as well as malignancy.With continued improvement in post-transplant survival rates, providing complex care for such long-term recipients as these will assume increasing clinical importance in the everyday practice of transplant medicine and these data highlight the problems to be anticipated.

    View details for DOI 10.1016/S1053-2498(03)00147-5

    View details for Web of Science ID 000188759100001

    View details for PubMedID 14761762

  • The impact of brain death on survival after heart transplantation: Time is of the essence TRANSPLANTATION Cantin, B., Kwok, B. W., Chan, M. C., Valantine, H. A., Oyer, P. E., Robbins, R. C., Hunt, S. A. 2003; 76 (9): 1275-1279


    It has been suggested that the modality of brain death and time from brain death until harvest impact survival and rejection after heart transplantation.Donor files from 475 adult heart-transplant recipients were examined. From these files, a total management time (time from incident leading to brain death until aortic cross clamp) was determined, and the cause of brain death was noted. Recipient characteristics, details of postoperative course, as well as survival were obtained from the Stanford University Medical Center Heart Transplantation Database.Two hundred and thirty (48.4%) donors sustained traumatic injuries, 112 (23.6%) suffered a subarachnoid hemorrhage, and 102 (21.4%) died of a gunshot wound to the head. The modality of brain death did not influence medium and long-term survival. A management time longer than 72 hours was associated with poorer outcome of the heart-transplant recipients. There were significantly more treated rejection episodes in recipients whose donor sustained traumatic injuries.Modality of brain death does not impact survival but appears to influence rejection. Increased management time is associated with adverse survival trends in heart-transplant recipients.

    View details for DOI 10.1097/01.TP.0000093445.50624.5A

    View details for Web of Science ID 000186653100001

    View details for PubMedID 14627902

  • Longer-term risks associated with 10-year survival after heart transplantation in the cyclosporine era JOURNAL OF HEART AND LUNG TRANSPLANTATION Shiba, N., Chan, M. C., Valantine, H. A., Gao, S. Z., Robbins, R. C., Hunt, S. A. 2003; 22 (10): 1098-1106


    Long-term survival after heart transplantation is common in the cyclosporine era. However, there are few data documenting pre-transplant/peri-operative factors predictive of truly long-term survival (>10 years). The purpose of this study is to identify factors associated with 10-year survival after heart transplantation.Our study population included 197 adults who survived >6 months and died <10 years after heart transplant (medium-term group) and 140 adults who survived >10 years after heart transplant (long-term group) between December 1980 and May 2001. A comparison was done between the two groups and we used multivariate analysis to identify which factors predicted 10-year survival.The long-term group had younger recipient and donor age, lower recipient body mass index at transplant, shorter waiting time and lower percentages of ischemic etiology/male recipient/non-white recipient. Kaplan-Meier plots of freedom from graft coronary artery disease and malignancy showed later onset patterns in the long-term group compared with the medium-term group. Multivariate analysis showed that white recipient, younger recipient and lower recipient body mass index at heart transplant were factors significantly associated with 10-year survival.Several pre-transplant/peri-operative factors were associated with survival beyond 10 years after heart transplantation. Stratified/tailored strategies based on these factors may be helpful to attain longer-term survival of recipients with higher risks.

    View details for DOI 10.1016/S1053-2498(02)01192-0

    View details for Web of Science ID 000185764400004

    View details for PubMedID 14550819

  • Simultaneous assessment of fractional and coronary flow reserves in cardiac transplant recipients - Physiologic investigation for transplant arteriopathy (PITA study) CIRCULATION Fearon, W. F., Nakamura, M., Lee, D. P., Rezaee, M., Vagelos, R. H., Hunt, S. A., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2003; 108 (13): 1605-1610


    The utility of measuring fractional flow reserve (FFR) to assess cardiac transplant arteriopathy has not been evaluated. Measuring coronary flow reserve (CFR) as well as FFR could add information about the microcirculation, but until recently, this has required two coronary wires. We evaluated a new method for simultaneously measuring FFR and CFR with a single wire to investigate transplant arteriopathy.In 53 cases of asymptomatic cardiac transplant recipients without angiographically significant coronary disease, FFR and thermodilution-derived CFR (CFRthermo) were measured simultaneously with the same coronary pressure wire in the left anterior descending artery and compared with volumetric intravascular ultrasound (IVUS) imaging. The average FFR was 0.88+/-0.07; in 75% of cases, the FFR was less than the normal threshold of 0.94; and in 15% of cases, the FFR was < or =0.80, the upper boundary of the gray zone of the ischemic threshold. There was a significant inverse correlation between FFR and IVUS-derived measures of plaque burden, including percent plaque volume (r=0.55, P<0.0001). The average CFRthermo was 2.5+/-1.2; in 47% of cases, CFRthermo was < or =2.0. In 14%, the FFR was normal (> or =0.94) and the CFR was abnormal (<2.0), suggesting predominant microcirculatory dysfunction.FFR correlates with IVUS findings and is abnormal in a significant proportion of asymptomatic cardiac transplant patients with normal angiograms. Simultaneous measurement of CFR with the same pressure wire, with the use of a novel coronary thermodilution technique, is feasible and adds information to the physiological evaluation of these patients.

    View details for DOI 10.1161/01.CIR.0000091116.84926.6F

    View details for Web of Science ID 000185624500027

    View details for PubMedID 12963639

  • Post-operative conversion from cyclosporine to tacrolimus in heart transplantation: A single-center experience JOURNAL OF HEART AND LUNG TRANSPLANTATION Cantin, B., Kwok, B. W., Shiba, N., Valantine, H. A., Hunt, S. A., Chan, M. C. 2003; 22 (7): 723-730


    Tacrolimus is a potent calcineurin inhibitor that was introduced to heart transplantation in the early 1990s. The side-effect profile of tacrolimus is more favorable than that of cyclosporine and some reports have suggested an advantage of tacrolimus in the treatment of rejection. The present study was undertaken to determine whether a late conversion to tacrolimus affords these benefits to heart transplant recipients.Charts from 109 patients who underwent conversion from cyclosporine to tacrolimus for recurrent rejection or adverse effects were retrospectively reviewed.During the year after conversion to tacrolimus, there was a significant decrease in treated rejection episodes. Conversion to tacrolimus rapidly resulted in an improved lipid profile. Two years after conversion blood pressure was significantly reduced. Apart from rejection, these benefits were found mainly among individuals converted to tacrolimus within 1 year of heart transplantation.Conversion from cyclosporine to tacrolimus is safe and results in a more favorable risk factor profile. However, most of the benefits are seen in individuals converted within 1 year of transplantation.

    View details for DOI 10.1016/S1053-2498(02)00647-2

    View details for Web of Science ID 000184235800003

    View details for PubMedID 12873539

  • Long-term results of heart transplantation in patients older than 60 years JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Demers, P., Moffatt, S., Oyer, P. E., Hunt, S. A., Reitz, B. A., Robbins, R. C. 2003; 126 (1): 224-231


    Advanced age has been traditionally considered a relative contraindication for heart transplantation. Older patients are now considered as potential candidates for heart transplantation. The objective of this study was to evaluate the long-term results of heart transplantation in patients older than 60 years.Between 1986 and 2001, 81 patients aged between 60 and 70 years (mean, 63 +/- 2 years) underwent heart transplantation. These patients were compared with 403 adult recipients younger than 60 years (mean, 47 +/- 11 years) who underwent transplantation during the same period.Thirty-day mortality was 6% (5/81) and 6% (25/403) in the older and younger patients, respectively (P = NS). Actuarial survival at 1, 5, and 10 years was 88% +/- 4% versus 83% +/- 2%, 75% +/- 5% versus 69% +/- 2%, and 50% +/- 9% versus 51% +/- 3% in the older and younger patients, respectively (P = NS). Older patients had significantly fewer rejection episodes (P =.003). Freedom from allograft coronary artery disease at 1, 5, and 10 years was 98% +/- 2% versus 92% +/- 2%, 85% +/- 6% versus 76% +/- 3%, and 81% +/- 7% versus 68% +/- 3% (P =.1). The incidences of infectious complication, cytomegalovirus infection, and posttransplant lymphoproliferative disorder were similar between the 2 groups, but older recipients were more likely to have a nonposttransplant lymphoproliferative disorder cancer (P =.002). Age at transplantation was not identified as an independent risk factor for early and late death.Heart transplantation in selected patients aged 60 years and older results in survival comparable with that of younger patients. Older patients have a lower risk of rejection but an increased risk of development of a nonposttransplant lymphoproliferative disorder cancer. Advanced age per se should not be considered as an exclusion criterion for transplantation.

    View details for DOI 10.1016/S0022-5223(03)00055-2

    View details for Web of Science ID 000184365400028

    View details for PubMedID 12878959

  • Effect of a change in gender on coronary arterial size - A longitudinal intravascular ultrasound study in transplanted hearts JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Herity, N. A., Lo, S., Lee, D. P., Ward, M. R., Filardo, S. D., Yock, P. G., Fitzgerald, P. J., Hunt, S. A., Yeung, A. C. 2003; 41 (9): 1539-1546


    We sought to document whether a physiologic change in gender has any effect on coronary arterial size.The coronary arteries are smaller in women, even after correction for body surface area (BSA). These differences may contribute to adverse clinical outcomes after coronary artery bypass graft surgery and myocardial infarction in women. In male and female transsexuals, pharmacologic doses of estrogens and androgens significantly influence vascular diameter. Thus, gender differences in the coronary vasculature may be a reflection of the hormonal environment.In 86 patients who had undergone orthotopic heart transplantation, serial intravascular ultrasound studies of the proximal left anterior descending coronary artery (LAD) were analyzed. Changes in vessel area (VA) over the first or second post-transplant year were recorded, and comparisons were made between donor hearts that were transplanted in a patient of the same gender and those that were transplanted in a patient of the opposite gender.Vessel area of the proximal LAD increased over time in all patient groups. In hearts transplanted within the same gender and in male donor hearts transplanted to female recipients, the change was small and not significant. However, in hearts transplanted from female donors to male recipients, there was a substantial and highly significant increase in LAD VA (median 16.13 to 17.88 mm(2); p = 0.01). This increase was not explained by confounding due to changes in BSA or left ventricular wall thickness.This pattern of arterial remodeling early after heart transplantation supports a link between host gender and coronary arterial size.

    View details for DOI 10.1016/S0735-1097(03)00246-8

    View details for Web of Science ID 000182631800019

    View details for PubMedID 12742295

  • Malignancy in organ transplantation: Heart TRANSPLANTATION PROCEEDINGS Hunt, S. A. 2002; 34 (5): 1874-1876

    View details for Web of Science ID 000177369700211

    View details for PubMedID 12176610

  • Conversion of cyclosporine to tacrolimus for refractory or persistent myocardial rejection TRANSPLANTATION PROCEEDINGS Chan, M. C., Kwok, B. W., Shiba, N., Cantin, B., Valantine, H. A., Hunt, S. A. 2002; 34 (5): 1850-1852

    View details for Web of Science ID 000177369700202

    View details for PubMedID 12176601

  • Long-term follow-up after total lymphoid irradiation in pediatric heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Chin, C., Hunt, S., Robbins, R., Hoppe, R., Reitz, B., Bernstein, D. 2002; 21 (6): 667-673


    Total lymphoid irradiation (TLI) is used to treat recurrent allograft rejection. Short-term success and complication rates have been reported in pediatric and adult cardiac transplant populations. We report the long-term efficacy and safety of TLI in treating intractable rejection in pediatric patients.Eight pediatric patients were treated with TLI (7 for recurrent rejection, 1 for risk of medication non-compliance). Therapy consisted of a mid-plane dose of 8 Gy administered with a 6-MeV linear accelerator using an anterior-posterior opposed technique. We reviewed outcomes for a total of 40 patient-years of follow-up.We encountered rejection (>Grade 2 by International Society for Heart and Lung Transplantation criteria) in 56.7% +/- 34.7% of biopsies performed within 90 days before TLI. Rejection rates dropped to 3.1% +/- 8.8% within the first 90 days (p < 0.005) after therapy and remained low at 5.6% +/- 1.3% (p < 0.05) during the first year after completion of TLI. Median time from TLI to the first subsequent rejection episode was 305 days (range, 77-1,920 days). Long-term follow-up (>3 years) of 5 patients demonstrated a continuing low incidence of rejection. Non-Hodgkin's lymphoma was diagnosed in 1 of 8 patients, graft coronary artery disease in 4 of 8 patients, and restrictive cardiomyopathy in 1 of 8 patients after TLI.Total lymphoid irradiation is an effective treatment for recurrent rejection and has short- and long-term efficacy. Morbid events may include cancer, graft coronary artery disease, and restrictive cardiomyopathy.

    View details for Web of Science ID 000176074500008

    View details for PubMedID 12057700

  • Mycophenolic acid concentrations in long-term heart transplant patients: relationship with calcineurin antagonists and acute rejection CLINICAL TRANSPLANTATION Cantin, B., Giannetti, N., Parekh, H., Panchal, S. N., Kwok, B. W., Najem, R., Woodman, K., Hunt, S. A., Valantine, H. A. 2002; 16 (3): 196-201


    When used in conjunction with steroids and cyclosporin, mycophenolate mofetil (MMF) has been shown to significantly reduce mortality and incidence of rejection in the first year after heart transplantation. It also appears that in this early post-transplantation period, the monitoring of immunosuppressive therapies may be warranted. The current study was undertaken to determine if such monitoring is still useful more than 1 yr after heart transplantation.Twenty-six patients who had survived the first year after orthotopic heart transplantation and had been on MMF therapy for more than 3 months were prospectively followed. At the time of their routine endomyocardial biopsy blood samples were taken to monitor immunosuppressive therapy. Most patients had two samples taken, on average 109 d apart.There were 22 episodes of asymptomatic rejection documented on a total of 48 biopsies. Of these, only two were of ISHLT (International Society for Heart and Lung Transplantation) grade 3A the remainder being of ISHLT grades 1 or 2. There was no relation between immunosuppressive regimen (tacrolimus and MMF or cyclosporin and MMF) and rejection. There was no relation between monitored immunosuppressive levels and rejection. Patients with the combination of MMF and tacrolimus had significantly higher plasma mycophenolic acid levels despite significantly lower daily MMF dose.There does not appear to be a benefit in continued monitoring of plasma mycophenolic acid levels beyond the first year of heart transplantation. There were significant differences in plasma mycophenolic acid levels depending on the type of calcineurin inhibitor concomitantly used.

    View details for Web of Science ID 000176236300008

    View details for PubMedID 12010143

  • Comment--the REMATCH trial: Long-term use of a left ventricular assist device for end-stage heart failure. Journal of cardiac failure Hunt, S. A. 2002; 8 (2): 59-60


    Implantable left ventricular assist devices (LVADs) have been used primarily as bridges to cardiac transplantation, although some patients have been maintained long term on these devices and a few have recovered enough to be weaned. This trial was designed to evaluate their suitability as long-term myocardial replacement therapy in patients who are ineligible for cardiac transplantation.One hundred twenty-nine patients with end-stage heart failure who were ineligible for cardiac transplantation were randomly assigned to receive an LVAD (Thoratec HeartMate; Thoratec, Pleasanton, CA) or optimal medical therapy, with a primary end point of all-cause mortality. To be eligible, patients had to have New York Heart Association (NYHA) class IV heart failure for at least 90 days despite attempted therapy with an angiotensin-converting enzyme inhibitor, diuretics, and digoxin; an ejection fraction

    View details for PubMedID 12016626

  • Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation - A comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone TRANSPLANTATION Valantine, H. A., Luikart, H., Doyle, R., Theodore, J., Hunt, S., Oyer, P., Robbins, R., Berry, G., Reitz, B. 2001; 72 (10): 1647-1652


    Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclovir compared with placebo in seronegative recipients of hearts from seropositive donors (D+/R-). This study tests the hypothesis that a combination of ganciclovir plus CMV hyperimmune globulin (CMVIG) is more effective than ganciclovir alone for preventing acute CMV illness and its long-term sequelae.The study population receiving CMVIG (n=80) included 27 heart transplant recipients (D+/R-) and 53 heart-lung and lung transplant recipients (R+ and/or D+). Each group was matched with historical controls who underwent transplantation within the preceding 2-3 years. Outcome measures compared were as follows: 3-year incidence of CMV disease; fungal infection; acute rejection; survival; rates and severity of transplant coronary artery disease (in heart patients) defined by intimal thickness (ultrasound) and coronary artery stenosis (angiographic); and incidence and death from obliterative bronchiolitis defined by pathological criteria on endobronchial biopsy specimens (in heart-lung/lung patients).Patients treated with CMVIG had a higher disease-free incidence of CMV, lower rejection incidence, and higher survival rate compared with the patients treated with ganciclovir alone. The coronary artery intimal thickness and the prevalence of intimal thickening were lower in the patients receiving CMVIG. Heart-lung and lung transplant patients treated with CMVIG had lower incidences of obliterative bronchiolitis and death from obliterative bronchiolitis and longer survival compared with the patients treated with ganciclovir alone.CMVIG plus ganciclovir seems to be more effective that ganciclovir alone for preventing the sequelae of CMV infection. A prospective randomized study is required to confirm these observations.

    View details for Web of Science ID 000172614200012

    View details for PubMedID 11726825

  • Mild hyperhomocysteinemia is not associated with cardiac allograft coronary disease CLINICAL TRANSPLANTATION Giannetti, N., Herity, N. A., Alimollah, A., Gao, S. Z., Schroeder, J. S., Yeung, A. C., Hunt, S. A., Valantine, H. A. 2001; 15 (4): 247-252


    Hyperhomocysteinemia is an independent risk factor for coronary disease and elevated plasma homocysteine levels have been documented in heart transplant recipients. The aim of this study was to test the hypothesis that homocysteine levels are associated with presence or absence of transplant coronary artery disease.Forty-three non-smoking adults were recruited, all of whom had received a heart transplant between 2 and 7 yr previously. All 43 had blood drawn for fasting homocysteine level on the day of presentation. All patients had undergone diagnostic coronary angiography within the past 6 months.For all patients, the average fasting plasma homocysteine level was 17.0+/-SD 6.6 micromol/L with a range from 6.0 to 36.9 micromol/L. Twenty-six patients (60%) had fasting plasma homocysteine levels above 15.0 micromol/L. On the basis of arteriography, patients were categorized as those with angiographically normal (n=22) or abnormal (n=21) coronary arteries. There was no difference in the mean plasma homocysteine level comparing patients with angiographically normal (17.2+/-SD 7.0 micromol/L) to those with abnormal (16.8+/-SD 6.2 micromol/L) coronary arteries. Plasma homocysteine levels increased with increasing plasma creatinine levels (r=0.63, p<0.0001) and with decreasing vitamin B6 levels (r=-0.56, p<0.0001).Mild hyperhomocysteinemia is a consistent finding among heart transplant recipients. This finding was not associated with transplant coronary artery disease in our patients. The combination of renal dysfunction and vitamin B6 deficiency may explain the unusual prevalence of hyperhomocysteinemia in heart transplant recipients.

    View details for Web of Science ID 000170338600005

    View details for PubMedID 11683818

  • Metabolic abnormalities characteristic of dysmetabolic syndrome predict the development of transplant coronary artery disease - A prospective study CIRCULATION Valantine, H., Rickenbacker, P., Kemna, M., Hunt, S., CHEN, Y. D., Reaven, G., Stinson, E. B. 2001; 103 (17): 2144-2152


    This study examines the hypothesis that metabolic abnormalities of dysmetabolic syndrome are risk factors for transplant coronary artery disease (TxCAD).Sixty-six patients without overt diabetes, 2 to 4 years after surgery, underwent intracoronary ultrasound (ICUS), measurement of plasma glucose and insulin after oral glucose (75 g), and fasting lipid and lipoproteins. TxCAD incidence by angiography or autopsy was prospectively determined during subsequent follow-up (8 years). Coronary artery intimal thickness (IT) and subsequent outcomes were compared in patients stratified as having "high" versus "low" plasma glucose (>8.9 mmol/L) and insulin (>760 pmol/L) 2 hours after glucose challenge; and "abnormal" versus "normal" fasting lipid and lipoprotein concentrations as defined by the National Cholesterol EducationPatients with high glucose or insulin concentrations had greater IT: 0.38+/-0.05 versus 0.22+/-0.02 mm, P0.3 mm than with IT

    View details for Web of Science ID 000168583700005

    View details for PubMedID 11331254

  • ACC/AHA tuidelines for the evaluation and management of chronic heart failure in the adult: executive summary J Am Coll Cardiol Hunt SA, Baker DW, Chin MH et al 2001; 38 (7): 2101-13
  • Who and when to consider for heart transplantation. Cardiology in review Hunt, S. A. 2001; 9 (1): 18-20


    The number of patients who are potentially eligible for heart transplantation is increasing steadily in the face of a plateaued or stable donor supply. Therefore, development of fair, sensible, and consistently and widely applied criteria for transplant recipient selection is a crucial medical and societal issue. This article examines the evolution of these criteria and advocates a flexible approach to their continued evolution.

    View details for PubMedID 11174911

  • Neoplasia after heart transplantation. Cardiology in review Kwok, B. W., Hunt, S. A. 2000; 8 (5): 256-259


    Transplant recipients have a higher incidence of cancer compared with the general population. This increased risk is related to the intensity and chronicity of immunosuppression that these patients receive. The common types and presentations of posttransplant tumors are reviewed and discussed. Regular surveillance is of paramount importance in detecting such tumors. Treatment invariably includes attempts to reduce immunosuppression.

    View details for PubMedID 11174903

  • New immunosuppressive agents in clinical use: mycophenolate mofetil and tacrolimus. Cardiology in review Hunt, S. A. 2000; 8 (3): 180-184


    Since the early 1980s, a 3-drug regimen that includes cyclosporine, azathioprine, and usually corticosteroids has been the mainstay of immunosuppression for patients undergoing cardiac transplantation. This regimen, however, has a variety of inherent toxicities and is not associated with any lesser incidence of graft coronary artery disease than the earlier regimen. For these reasons, there has been a widely perceived need for the introduction of improved immunosuppressive agents. Two such agents have thus far been introduced into clinical organ transplantation: mycophenolate mofetil and tacrolimus. Mycophenolate mofetil is used as a substitute for azathioprine and has been shown to result in significantly lower mortality rates and freedom from rejection in heart transplant recipients. Tacrolimus can be used as a substitute for cyclosporine but (at least in the short-term) seems to offer no important advantage in terms of survival or rejection. The combination of these 2 new agents seems to have no short-term disadvantage and longer-term follow-up is pending.

    View details for PubMedID 11174892

  • Determinants of coronary remodeling in transplant coronary disease - A simultaneous intravascular ultrasound and Doppler flow study CIRCULATION Schwarzacher, S. P., Uren, N. G., Ward, M. R., Schwarzkopf, A., Giannetti, N., Hunt, S., Fitzgerald, P. J., Oesterle, S. N., Yeung, A. C. 2000; 101 (12): 1384-1389


    Coronary remodeling plays a significant role in lumen loss in transplant allograft vasculopathy (TxCAD), but the determinants of remodeling are unknown. We assessed the relationship between remodeling and plaque topography, coronary compliance, and blood flow in TxCAD.One artery in each of 27 transplant patients was investigated with simultaneous intravascular ultrasound and coronary flow measurements (basal and hyperemic by Doppler flow wire). At 4 to 8 different cross sections (mean 5.1+/-1. 2), plaque topography (concentric or eccentric) was determined, and total vessel area, lumen area, and intimal/medial area (IMA) were measured. Mean remodeling ratio (vessel area/IMA) in eccentric lesions (E, n=28) was significantly larger than that in concentric lesions (C, n=70) (E 5.87+/-0.93 versus C 3.58+/-0.62; P<0.001), despite similar IMA (E 3.89+/-0.68 versus C 3.90+/-0.41; P=NS) and distribution of imaged segments. Remodeling ratio was consistently larger in eccentric lesions in all 3 vessel segments when analyzed separately, and mean remodeling ratio for each artery was larger in vessels with predominantly eccentric lesions. Coronary compliance ([Delta lumen area/diastolic lumen area]/Delta mean arterial pressure x 10(3)) was also significantly greater in eccentric lesions versus concentric lesions (proximal 1.00+/-0.39 versus 0.22+/-0.04; mid 0.71+/-0.17 versus 0.21+/-0.10; distal 0.43+/-0.13 versus 0. 01+/-0.08; all P<0.01). Coronary flow reserve was also significantly higher in coronary arteries with primarily eccentric lesions (E 2. 49+/-0.64 versus C 1.87+/-0.28; P<0.01).Vessel remodeling in transplant vasculopathy is significantly greater in eccentric lesions than in concentric lesions, possibly due to greater coronary compliance and resistive vessel function.

    View details for Web of Science ID 000086143700014

    View details for PubMedID 10736281

  • Primary bronchogenic carcinoma after heart or lung transplantation: Radiologic and clinical findings JOURNAL OF THORACIC IMAGING Choi, Y. H., Leung, A. N., Miro, S., Poirier, C., Hunt, S., Theodore, J. 2000; 15 (1): 36-40


    Chronic immunosuppression in organ transplant recipients predisposes to the development of malignant disease. The authors describe their 29-year institutional experience of bronchogenic carcinoma developing after heart and lung transplantation. Seven cases of bronchogenic carcinoma were diagnosed in 1,119 heart and lung transplant recipients. Computed tomography scans and radiographs at time of diagnosis, as well as prior radiographs available in six patients were retrospectively analyzed by two radiologists in consensus. The seven cases involved six heart and one lung transplant recipients. Six patients were smokers with a mean smoking history of 66 pack-years. Mean time interval from transplantation to cancer detection was 25 months. Radiologic findings consisted of a solitary pulmonary nodule (n = 3), mass with satellite nodules (n = 1), and obstructive pneumonitis (n = 1). In the sixth patient, the cancer was not radiographically visible because of obscuration by adjacent fibrosis. On review, radiographic abnormalities were present a mean of 12 months prior to diagnosis in 66% of patients. In the heart or lung transplant population, bronchogenic carcinoma develops in recipients with extensive smoking histories. It presents radiographically as a nodule, mass, or obstructive pneumonitis, and is usually visible on radiographs before the time of diagnosis.

    View details for Web of Science ID 000084709000008

    View details for PubMedID 10634661

  • Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis - A post hoc analysis of a randomized, placebo-controlled study CIRCULATION Valantine, H. A., Gao, S. Z., Menon, S. G., Renlund, D. G., Hunt, S. A., Oyer, P., Stinson, E. B., Brown, B. W., Merigan, T. C., Schroeder, J. S. 1999; 100 (1): 61-66


    Coronary artery disease occurs in an accelerated fashion in the donor heart after heart transplantation (TxCAD), but the cause is poorly understood. The risk of developing TxCAD is increased by cytomegalovirus (CMV) infection and decreased by use of calcium blockers. Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness, and we now propose to determine whether this therapy also prevents TxCAD.One hundred forty-nine consecutive patients (131 men and 18 women aged 48+/-13 years) were randomized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation. Immunosuppression consisted of muromonab-CD3 (OKT-3) prophylaxis and maintenance with cyclosporine, prednisone, and azathioprine. Mean follow-up time was 4.7+/-1.3 years. In a post hoc analysis of this trial designed to assess efficacy of ganciclovir for prevention of CMV disease, we compared the actuarial incidence of TxCAD, defined by annual angiography as the presence of any stenosis. Because calcium blockers have been shown to prevent TxCAD, we analyzed the results by stratifying patients according to use of calcium blockers. TxCAD could not be evaluated in 28 patients because of early death or limited follow-up. Among the evaluable patients, actuarial incidence of TxCAD at follow-up (mean, 4.7 years) in ganciclovir-treated patients (n=62) compared with placebo (n=59) was 43+/-8% versus 60+/-10% (P<0.1). By Cox multivariate analysis, independent predictors of TxCAD were donor age >40 years (relative risk, 2.7; CI, 1.3 to 5.5; P<0.01) and no ganciclovir (relative risk, 2.1; CI, 1.1 to 5.3; P=0.04). Stratification on the basis of calcium blocker use revealed differences in TxCAD incidence when ganciclovir and placebo were compared: no calcium blockers (n=53), 32+/-11% (n=28) for ganciclovir versus 62+/-16% (n=25) for placebo (P<0.03); calcium blockers (n=68), 50+/-14% (n=33) for ganciclovir versus 45+/-12% (n=35) for placebo (P=NS).TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.

    View details for Web of Science ID 000081279300013

    View details for PubMedID 10393682

  • Current status of cardiac transplantation JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Hunt, S. A. 1998; 280 (19): 1692-1698


    Cardiac transplantation, first introduced 30 years ago, has become a widely used and increasingly important procedure for treatment of truly end-stage heart disease. Current use is limited strictly by donor supply, making selection of appropriate recipients an important ethical and societal issue. Survival rates after transplantation rose in the 1980s with the use of cyclosporine and have remained relatively consistent since then, although recipients older than 65 years or younger than 1 year have lower survival rates than recipients of other ages. Although immunosuppressive drugs have helped establish cardiac transplantation as a successful procedure, risks of opportunistic infection and rejection, as well as coronary arteriopathy, have led to development of new immunosuppressive agents currently under study. Future alternatives to the current technology of cardiac allotransplantation may include xenotransplantation and/or nonbiological replacement of the heart with mechanical devices.

    View details for Web of Science ID 000076980700036

    View details for PubMedID 9832002

  • Mechanical circulatory support and cardiac transplantation CIRCULATION Hunt, S. A., Frazier, O. H., Myers, T. J. 1998; 97 (20): 2079-2090

    View details for Web of Science ID 000073757200014

    View details for PubMedID 9610540

  • Heart Retransplantation. Cardiology in review Chan, M., Hunt, S. A. 1998; 6 (6): 350-355


    Retransplantation of the heart is not a widely performed procedure, and few centers have large series. The most common indication for heart retransplantation is transplant graft coronary artery disease, followed by acute rejection and primary graft dysfunction. The outcome after heart retransplantation is not as good as with primary transplantation; the one year actuarial survival rate is lower and there are more perioperative complications. The number of episodes of infection and rejection, however, is not increased. The outcome of heart retransplantation for transplant graft coronary artery disease is better than that of retransplantation for rejection or primary graft failure. However, it is still inferior to that of primary heart transplantation. Because of this and the critical shortage of donor hearts, it is suggested that heart retransplantation should be limited to carefully selected patients.

    View details for PubMedID 10348959

  • Importance of decreased heart rate in predicting transplant coronary artery disease CLINICAL TRANSPLANTATION Gullestad, L., Ross, H., Myers, J., Hoang, K., Hunt, S., Stinson, E. B., Valentine, H. A. 1997; 11 (6): 628-632


    Studies in animals and humans have demonstrated that an increased heart rate is a predictor for the development of coronary atherosclerosis and overall cardiovascular mortality. In contrast, we have previously reported that the need for pacemaker implantation because of bradycardia in heart transplant recipients is associated with an increased prevalence of transplant coronary artery disease (TxCAD). Hence, the relevance of changes in heart rate to the development of TxCAD remains unclear. Intra-coronary ultrasound examinations (ICUS) were therefore analyzed in 130 heart transplant recipients (age 50 +/- 11 yr) studied at annual evaluations (3.7 +/- 3.0 yr after transplantation). Quantitative ultrasound measurements were obtained by calculating mean coronary artery intimal thickness (MIT) obtained by examination of the left anterior descending artery. The presence of TxCAD was defined as MIT > 0.3 mm. Resting heart rates (HR) were recorded with the patients in the supine position during routine echocardiography. Based on HR recordings, two groups were defined: group 1, HR below; or group 2, HR above the median. TxCAD was detected in 40% of the ICUS studies overall. The prevalence of TxCAD was higher in group 1 (49%) compared with group 2 (33%), p < 0.05. There was no significant difference in donor ischemic time or donor gender, recipient age, gender, body weight, CMV status, creatinine, total cholesterol, use of lipid lowering drugs or diltiazem. Donor age and use of beta-blockers were higher in group 1 compared with group 2 (29 +/- 10 vs. 25 +/- 9 yr, and 15% vs. 5%, for donor age and beta-blocker use, respectively). By multivariate regression analysis only donor age and years after transplantation were independently correlated with TxCAD. After excluding patients taking beta-blockers and diltiazem, the prevalence of CAD was still higher in group 1 (50%) vs. group 2 (34%). In conclusion, transplant coronary artery disease is more prevalent in patients with lower, rather than higher, heart rates. The reason for this is unclear, but may reflect impaired blood flow to the sinoatrial node.

    View details for Web of Science ID A1997YK49400019

    View details for PubMedID 9408698

  • Relation of donor age and preexisting coronary artery disease on angiography and intracoronary ultrasound to later development of accelerated allograft coronary artery disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Gao, S. Z., Hunt, S. A., Alderman, E. L., Liang, D., Yeung, A. C., Schroeder, J. S. 1997; 29 (3): 623-629


    This study assessed the influence of donor age and preexisting donor coronary disease on the later development of allograft coronary artery disease, ischemic events and overall survival.The increasing demand for heart donors has led to a tendency to liberalize age criteria for donor acceptability.A total of 233 consecutive heart transplant recipients who had baseline, early postoperative and follow-up coronary angiograms, as well as a subset of 47 patients with baseline intracoronary ultrasound imaging recordings, were analyzed (mean 3.8 years of follow-up). Patients were subclassified according to the presence of donor coronary artery disease on the baseline angiogram and stratified at age 40 years.patients without evidence of preexisting coronary artery disease on a baseline angiogram (n = 219) were significantly less likely to develop new disease than the 14 patients with preexisting coronary artery disease (p = 0.002). Although older donors exhibited earlier coronary artery disease than younger donors at 3 years of follow-up, there was no difference by 5 years (p = 0.25). There was no difference in survival or probability of developing ischemic events between the groups. Baseline ultrasound imaging revealed substantial disease in 7 of 9 older donated hearts, and in only 7 of 38 younger donated hearts (p = 0.002). Preexisting coronary artery disease, nonuse of calcium channel blocking agents, older donor age, posttransplantation cytomegalovirus infection, elevated very low density lipoprotein levels and previous ischemic heart disease in the recipient were significant predictors of allograft coronary artery disease.Heart donors with angiographic evidence of preexisting coronary artery disease and older donors are more likely to develop new allograft coronary artery disease by 3 years. However, there is no difference in survival or freedom from ischemic events between younger and older donors at a mean follow-up of 3.8 years.

    View details for Web of Science ID A1997WL49000023

    View details for PubMedID 9060902

  • Methotrexate or total lymphoid radiation for treatment of persistent or recurrent allograft cellular rejection: A comparative study JOURNAL OF HEART AND LUNG TRANSPLANTATION Ross, H. J., Gullestad, L., Pak, J., Slauson, S., Valantine, H. A., Hunt, S. A. 1997; 16 (2): 179-189


    Methotrexate and total lymphoid irradiation (TLI) have been used successfully for treatment of recurrent and persistent rejection in orthotopic heart transplant recipients; however, there has been no comparison of these two modalities.We retrospectively compared the efficacy of methotrexate (n = 29) versus TLI (n = 28) in heart transplant recipients with recurrent or persistent rejection. All patients received induction therapy (rabbit anti-thymocyte globulin or OKT3) and standard triple immunosuppressive therapy. Methotrexate (7.5 mg to 22.5 mg per wk) or TLI (80 cGy x 10 fractions) was used for the treatment of recurrent or persistent rejection on the basis of clinical indications. Average biopsy scores (International Society of Heart and Lung Transplantation biopsy score/total number of biopsies performed) calculated over 3-month periods, daily maintenance prednisone dose before and after methotrexate or TLI treatment, and actuarial survival and freedom from angiographic coronary artery disease and infection were compared. To control for the general decrease in prednisone with increased time from transplantation, a control group matched for time from transplantation was selected.Recipient sex and age at transplant, donor age, and donor ischemic time were similar in both groups. Days after transplantation to start of therapy was longer in patients receiving methotrexate; however, this did not reach statistical significance. Patients receiving TLI had received more cumulative corticosteroids and OKT3 before the start of TLI therapy (p < 0.001). There were no differences in actuarial freedom from infection or coronary artery disease between the two groups and between the treatment groups and the control group. Actuarial survival was reduced in patients receiving TLI 3 years after transplantation (p < 0.05). Maintenance prednisone doses from 3 months before until 9 months after therapy (mg/kg) were not different between patients receiving TLI and methotrexate and were significantly greater than the prednisone doses in the control group. Four months after treatment initiation, the prednisone dose was significantly reduced in both treatment groups compared with the pretherapy dose (methotrexate 0.28 +/- 0.16 to 0.22 +/- 0.13, p = 0.05; TLI 0.36 +/- 0.16 to 0.22 +/- .07, p < 0.001). The average biopsy score was significantly reduced by both methotrexate and TLI therapy (methotrexate 1.8 +/- 0.7 to 0.83 +/- 0.9, p = 0.0001; TLI 2.1 +/- 0.8 to 1.0 +/- 0.9, p = 0.0001).Methotrexate and TLI are both effective for the treatment of recurrent or persistent rejection after heart transplantation, reducing average biopsy scores and daily maintenance prednisone doses. There was a reduction in actuarial survival rates in patients treated with TLI, possibly reflecting the greater rejection therapy received before TLI initiation. Because both agents are effective, the choice of methotrexate or TLI may be based on clinical indications, as well as other issues, such as cost, compliance, and availability.

    View details for Web of Science ID A1997WL96500004

    View details for PubMedID 9059929

  • Early Doppler echocardiographic: Dysfunction is associated with an increased mortality after orthotopic cardiac transplantation CIRCULATION Ross, H. J., Gullestad, L., Hunt, S. A., TOVEY, D. A., PURYEAR, J. B., McMillan, A., Stinson, E. B., Valantine, H. A. 1996; 94 (9): 289-293
  • Early Doppler echocardiographic dysfunction is associated with an increased mortality after orthotopic cardiac transplantation. Circulation Ross, H. J., Gullestad, L., Hunt, S. A., TOVEY, D. A., PURYEAR, J. B., McMillan, A., Stinson, E. B., Valantine, H. A. 1996; 94 (9): II289-93


    Doppler echocardiographic (DE) diastolic dysfunction has been correlated with rejection after orthotopic cardiac transplantation (Tx). However, the relationship of early diastolic dysfunction to late outcome is unknown. The purpose of this study was to assess the correlation between early DE diastolic dysfunction and outcome after heart Tx.Of 133 patients undergoing heart Tx between October 1990 and April 1994, 83 were identified with > or = 4 routine DE performed during the first 6 months. Assessment of diastolic function included measurement of isovolumic relaxation time (IVRT), pressure half-time (PHT), and peak early mitral inflow velocity (M1). Diastolic dysfunction was defined as a decrease of 15% from baseline (IVRT and PHT) or an increase of 20% (M1). A mean dysfunction score (MDS) was calculated for each patient (number of episodes of dysfunction by Doppler total number of echocardiograms performed). The population diastole MDS was determined and two groups established (group 1, MDS < mean; group 2, MDS > mean). Actuarial survival, rejection, and transplant coronary artery disease (TxCAD) were compared between groups. Actuarial survival was significantly reduced in patients with greater early diastolic dysfunction (P < .05). There were 17 deaths overall: 5 in group 1 (mean, 786 days) and 12 in group 2 (mean, 384 days). There were no significant differences in treated rejection episodes, actuarial freedom from rejection or TxCAD, immunosuppression, sex, donor age, donor ischemic time, or cytomegalovirus between the two groups.Diastolic dysfunction within 6 months of transplant was associated with an increased late mortality.

    View details for PubMedID 8901762

  • Are heart-lung transplant recipients protected from developing transplant coronary artery disease? A case-matched intracoronary ultrasound study CIRCULATION Lim, T. T., Botas, J., Ross, H., Liang, D. H., Theodore, J., Hunt, S. A., Oesterle, S. N., Yeung, A. C. 1996; 94 (7): 1573-1577


    Accelerated coronary artery disease is a major cause of mortality in heart transplant recipients; however, it does not appear to play a major role in the clinical outcome of heart-lung transplant recipients. The purpose of this study was to determine whether the incidence and severity of transplant coronary artery disease as detected by intracoronary ultrasound in heart-lung transplant recipients are less than those encountered in heart transplant recipients.We studied the left anterior descending coronary artery with the use of intracoronary ultrasound imaging in 22 heart-lung transplant recipients at the time of their routine annual coronary angiogram. Twenty-two heart transplant recipients were case matched for number of years after transplant at ultrasound study, recipient age, donor age, and diagnosis of nonischemic cardiomyopathy. Mean intimal area, intimal index, Stanford class, and incidence of at least moderate disease (Stanford class > or = 3) were measured and calculated in each group and then compared between the two groups. Mean intimal area (1.6 +/- 2.5 versus 3.8 +/- 2.8 mm2), mean intimal index (0.07 +/- 0.10 versus 0.22 +/- 0.14), mean Stanford class (1.7 +/- 1.0 versus 2.7 +/- 1.2), and incidence of Stanford class > or = 3 (14% versus 45%) were significantly lower in the heart-lung transplant recipient group.The incidence and severity of transplant coronary artery disease are much less in patients receiving heart-lung transplants than in those receiving heart transplants alone.

    View details for Web of Science ID A1996VJ97900015

    View details for PubMedID 8840846

  • Early development of accelerated graft coronary artery disease: Risk factors and course JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Gag, S. Z., Hunt, S. A., Schroeder, J. S., Alderman, E. L., Hill, I. R., Stinson, E. B. 1996; 28 (3): 673-679


    This study assessed the time of first appearance of angiographic graft coronary artery disease in relation to clinical and laboratory variables and clinical events in heart transplant recipients.Graft coronary artery disease is the main factor limiting long-term survival after heart transplantation, and it is important to understand its natural history.One hundred thirty-nine consecutive patients who developed angiographic coronary artery disease after heart transplantation were classified according to early (< or = 2 years) versus late (> 2 years) posttransplantation initial detection of coronary artery disease. These subgroups were analyzed for differences in clinical and laboratory demographics, incidence of progression to ischemic events and incidence of antecedent cytomegalovirus infection.The early-onset group (64 patients) had more rapid progression to ischemic events than the late-onset group (75 patients), with 59% of the late group and only 35% of the early group free from ischemic events by 5 years after initial detection (p = 0.02), but there were no significantly correlated clinical or laboratory predictors of ischemic events. The early group had a significantly higher incidence of antecedent cytomegalovirus infection.We conclude that 1) accelerated graft coronary artery disease develops at variable times after heart transplantation; 2) the early appearance of graft coronary artery disease may be a marker of intrinsically more aggressive disease; 3) cytomegalovirus infection is associated with earlier onset of graft coronary artery disease. Patients with early development of graft coronary artery disease should potentially be given priority for interventional strategies as they are developed.

    View details for Web of Science ID A1996VE27300019

    View details for PubMedID 8772755

  • Induction of nitric oxide synthase in the human cardiac allograft is associated with contractile dysfunction of the left ventricle CIRCULATION Lewis, N. P., Tsao, P. S., Rickenbacher, P. R., Xue, C., Johns, R. A., Haywood, G. A., VONDERLEYEN, H., Trindade, P. T., Cooke, J. P., Hunt, S. A., Billingham, M. E., Valantine, H. A., Fowler, M. B. 1996; 93 (4): 720-729


    The mechanisms underlying cardiac contractile dysfunction after transplantation remain poorly defined. Previous work has revealed that inducible nitric oxide synthase (iNOS) is expressed in the rat heterotopic cardiac allograft during rejection; resultant overproduction of nitric oxide (NO) might cause cardiac contractile dysfunction via the negative inotropic and cytotoxic actions of NO. In this investigation, we tested the hypothesis that induction of iNOS may occur and be associated with cardiac allograft contractile dysfunction in humans.We prospectively studied 16 patients in the first year after cardiac transplantation at the time of serial surveillance endomyocardial biopsy. Clinical data, the results of biopsy histology, and echocardiographic and Doppler evaluation of left ventricular systolic and diastolic function were recorded. Total RNA was extracted from biopsy specimens, and mRNA for beta-actin, detected by reverse transcription-polymerase chain reaction (RT-PCR) using human specific primers, was used as a constitutive gene control; iNOS mRNA was similarly detected by RT-PCR using human specific primers. iNOS protein was detected in biopsy frozen sections by immunofluorescence. Myocardial cGMP was measured by radioimmunoassay, and serum nitrogen oxide levels (NOx = NO2 + NO3) were measured by chemiluminescence. iNOS mRNA was detected in allograft myocardium at some point in each patient and in 59 of 123 biopsies (48%) overall. In individual patients, iNOS mRNA expression was episodic and time dependent; the frequency of expression was highest during the first 180 days after transplant (P = .0006). iNOS protein associated with iNOS mRNA was detected by immunofluorescence in cardiac myocytes. iNOS mRNA expression was not related to the ISHLT histological grade of rejection or to serum levels of NOx but was associated with increased levels of myocardial cGMP (P = .01) and with both systolic (P = .024) and diastolic (P = .006) left ventricular contractile dysfunction measured by echocardiography and Doppler.These data support a relation between iNOS mRNA expression and contractile dysfunction in the human cardiac allograft.

    View details for Web of Science ID A1996TV05300015

    View details for PubMedID 8641001

  • Coronary artery intimal thickening in the transplanted heart - An in vivo intracoronary ultrasound study of immunologic and metabolic risk factors TRANSPLANTATION Rickenbacher, P. R., Kemna, M. S., Pinto, F. J., Hunt, S. A., Alderman, E. L., Schroeder, J. S., Stinson, E. B., Popp, R. L., Chen, I., Reaven, G., Valantine, H. A. 1996; 61 (1): 46-53


    This study examined the hypothesis that immunologic factors are the major correlates of coronary artery intimal thickening and luminal stenosis. The study population included 116 adult heart transplant recipients with a mean age of 44.7 +/- 12.0 years (89 men and 27 women) undergoing annual coronary angiography and intracoronary ultrasound 3.4 +/- 2.7 (range, 1.0-14.6) years after transplantation. Mean intimal thickness was obtained from several distinct sites along the left anterior descending and/or left circumflex coronary artery by intracoronary ultrasound. Coronary artery stenosis defined by angiography was classified as mild (< 30% luminal stenosis), moderate (> or = 30-70% luminal stenosis), or severe (> 70% luminal stenosis or diffuse pruning of distal vessels). Prevalence of any transplant coronary artery disease (TxCAD) was 85% by intracoronary ultrasound and 15% by angiography. By multiple regression analysis, only average fasting plasma triglyceride level (P < 0.006) and average weight (P < 0.007) were significantly correlated with severity of intimal thickening (R = 0.54, P < 0.0001). Donor age (P < 0.006) and average fasting plasma triglyceride level (P < 0.009) were significantly correlated with stenosis by angiography. Correlation of multiple immunologic and metabolic factors with intimal thickness by univariate analysis suggests a multifactorial etiology for TxCAD. Among the multiple univariate correlates of TxCAD, higher fasting plasma triglyceride levels and body weight are the only independent correlates of TxCAD. The absence of acute rejection as an independent predictor of intimal thickening suggests that mechanisms beyond those mediating typical cellular rejection should be targeted for advancing our understanding of Tx-CAD.

    View details for Web of Science ID A1996TQ20100011

    View details for PubMedID 8560573

  • PROGNOSTIC IMPORTANCE OF INTIMAL THICKNESS AS MEASURED BY INTRACORONARY ULTRASOUND AFTER CARDIAC TRANSPLANTATION CIRCULATION Rickenbacher, P. R., Pinto, F. J., Lewis, N. P., Hunt, S. A., Alderman, E. L., Schroeder, J. S., Stinson, E. B., Brown, B. W., Valantine, H. A. 1995; 92 (12): 3445-3452


    Although intracoronary ultrasound (ICUS) has been validated for the early detection of transplant coronary artery disease (TxCAD), the prognostic importance of findings detected by this new imaging technique is unknown.This study examined the relation of clinical outcome in 145 heart transplant recipients (mean age, 45.1 +/- 11.1 years) with the amount of intimal thickness measured by ICUS during routine annual coronary angiography 1 to 10 years (mean, 3.1 +/- 2.2 years) after transplantation. From published autopsy data, a mean intimal thickness of > 0.3 mm was considered significant. During a mean follow-up time of 48.2 +/- 10.2 months, 23 deaths (12 cardiac) occurred, and 6 patients required retransplantation. Angiographic TxCAD developed in 22 of 125 patients (17.6%) in the subgroup with normal angiograms at the time of ICUS and a follow-up annual angiographic study. In the total population and the subgroup, mean intimal thicknesses of > 0.3 and < or = 0.3 mm, respectively, were associated with significantly inferior 4-year actuarial overall survival (73% versus 96%, P = .005; 72% versus 92%, P = .05), cardiac survival (79% versus 96%, P = .005; 80% versus 98%, P = .04), and freedom from cardiac death and retransplantation (74% versus 98%, P < .0001; 70% versus 96%, P = .001). In addition, ICUS predicted freedom from development of subsequent angiographic TxCAD in the subgroup that was initially normal (26% versus 72%, P = .02). A mean intimal thickness by ICUS of > 0.3 mm was associated with inferior clinical outcome regardless of the presence of angiographic TxCAD and predicted the development of subsequent angiographic TxCAD. Despite significantly longer duration after transplantation, higher rejection incidence, and lower average daily cyclosporine dose, none of these covariates were independent risk factors for outcome.These findings confirm the prognostic importance of mean intimal thickening of > 0.3 mm in heart transplant recipients and suggest that these patients should be candidates for early interventional strategies.

    View details for Web of Science ID A1995TJ65500018

    View details for PubMedID 8521566

  • HEART RETRANSPLANTATION - THE 25-YEAR EXPERIENCE AT A SINGLE INSTITUTION JOURNAL OF HEART AND LUNG TRANSPLANTATION Smith, J. A., Ribakove, G. H., Hunt, S. A., Miller, J., Stinson, E. B., Oyer, P. E., Robbins, R. C., Shumway, N. E., Reitz, B. A. 1995; 14 (5): 832-839


    The current critical shortage of cardiac allograft donors means that the decision to offer a patient repeat heart transplantation must be carefully considered. Since 1968, a total of 66 heart retransplantation procedures (63 first-time and three second-time) have been performed in 63 patients at Stanford.There were 52 male and 11 female patients, ranging in age from 3 to 62 years with a mean age of 41 years. Indications for retransplantation were primary allograft failure in nine patients, acute rejection in 17, graft atherosclerosis in 37, and constrictive disease in three. Six of the seventeen patients (35%) who underwent retransplantation before 1981 died in the hospital, and none are currently alive. Of the 46 patients who underwent retransplantation since 1981 treated with cyclosporine-based immunosuppression, 11 (24%) died in the hospital. Actuarial survival estimates for the whole retransplantation group at 1, 5, and 10 years were 55% +/- 8%, 33% +/- 8%, and 22% +/- 7%, respectively.This survival was significantly worse (p < 0.05) than that in patients undergoing primary heart transplantation (81% +/- 2%, 62% +/- 2%, 44% +/- 13% at 1, 5, and 10 years). Those patients who underwent retransplantation for graft atherosclerosis since 1981 had a significantly better 1-year survival (p < 0.05) than those who underwent retransplantation for allograft rejection (69% +/- 10% versus 33% +/- 16%), but the 5-year survival was similar in both groups (34% +/- 11% versus 33% +/- 16%). Since 1981, actuarial freedoms from infection and rejection were 22% +/- 8% and 41% +/- 9%, respectively, at 1 year, and 7% +/- 7% and 36% +/- 9% at 5 years. Patients with cyclosporine-induced renal dysfunction (serum creatinine level of greater than 2.0 mg/dl) had a high probability of requiring postoperative dialysis and also of death after retransplantation. Three patients with significant cyclosporine-induced renal dysfunction underwent simultaneous kidney transplantation and heart retransplantation, and all were alive and well at the time this article was written. Sixteen patients were also currently alive at a mean follow-up of 44 months, and 15 were in New York Heart Association functional class I.We continue to list carefully selected candidates with good rehabilitation potential for heart retransplantation.

    View details for Web of Science ID A1995RY62700004

    View details for PubMedID 8800717



    The mechanisms responsible for transplant coronary artery disease (CAD) and its predisposing factors remain incompletely understood. The influence of donor characteristics as predisposing factors has not been studied systematically. We examined the correlation of donor demographic, clinical, and immunologic parameters with transplant CAD assessed by both intracoronary ultrasound (ICUS) and coronary angiography in 116 heart transplant recipients (age 44.7 +/- 12.0 years) studied 3.4 years (range 1.0 to 14.6) after transplantation. Quantitative ultrasound data were obtained by calculating mean intimal thickness from several distinct coronary sites. Coronary angiograms were categorized visually as normal or showing any transplant CAD. By multivariate regression analysis, donor undersize of > 20% of recipient weight (p < 0.02) and duration after transplantation (p < 0.005) were independently correlated with the amount of ICUS intimal thickness (r = 0.36, p = 0.0007), and older donor age with angiographic evidence for the disease (r = 0.34, p < 0.006). In a subgroup analysis of the 39 patients studied 1 year after transplantation, white donor race (p < 0.05), fewer human leukocyte antigen-DR mismatches (p < 0.002), shorter ischemic time (p < 0.04), and donor smoking history (p < 0.02) were independent predictors for severity of ICUS intimal thickening (r = 0.92, p = 0.0009); higher donor age (p < 0.006) and higher arterial partial pressure of oxygen (p < 0.003) were independent predictors for angiographic disease (r = 0.67, p < 0.002). In conclusion, donor characteristics may contribute to the probably multifactorial pathogenesis of transplant CAD.

    View details for Web of Science ID A1995RN75900005

    View details for PubMedID 7639157

  • CLINICAL OUTCOME OF INTERVAL CADAVERIC RENAL-TRANSPLANTATION IN CARDIAC ALLOGRAFT RECIPIENTS CLINICAL TRANSPLANTATION Kuo, P. C., Luikart, H., BUSSEHENRY, S., Hunt, S. A., Valantine, H. A., Stinson, E. B., Oyer, P. E., Scandling, J. D., Alfrey, E. J., Dafoe, D. C. 1995; 9 (2): 92-97


    The introduction of cyclosporine into widespread clinical use has resulted in improved patient survival following cardiac transplantation. As a result of increased numbers of cardiac transplants, the inherent nephrotoxicity of cyclosporine, and prolonged patient survival, cardiac transplant recipients commonly present with renal dysfunction. In the subgroup who ultimately develop end-stage renal disease (ESRD), therapeutic options include renal transplantation. However, the clinical course associated with this treatment modality is unknown. From 1980 to 1993, 430 cardiac transplants were performed with cyclosporine-based immunosuppression at the Standard University Medical Center. Fourteen (3.3%) patients developed ESRD, requiring chronic dialysis or renal transplantation. The cause of ESRD was cyclosporine nephropathy (13/14; 93%) and glomerulonephritis (1/14; 7%). The average time interval to the development of ESRD was 82 +/- 42 months. Nine patients underwent renal transplantation. During the period of followup (38 +/- 27 months; range 6-89 months) after renal transplantation, cardiac function remained stable. There were no episodes of primary nonfunction of the renal allograft. Patient and renal allograft survival was 89% at both 1 and 3 years after renal transplant. Average serum creatinine was 1.3 +/- 0.6 mg/dl at 1 year and 1.6 +/- 0.8 mg/dl at 3 years post-transplant. The incidence of infectious complications was not statistically different when compared to that of the heart transplant controls and that of a group of cadaveric renal transplant controls (n = 20). Surprisingly, the incidence of renal allograft rejection in the heart transplant patients was 10-fold less than that of the renal transplant controls (0.006 +/- 0.02/patient-year vs. 0.062 +/- 0.05/patient-year; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1995QV67600006

    View details for PubMedID 7599409



    Cardiac allograft vascular disease is characterized by accelerated and diffuse intimal proliferation involving both the microvasculature and epicardial vessels. Because in vivo documentation of this complication is now possible with intracoronary ultrasound imaging, we can examine the relationship of intimal proliferation to markers of immunity and endothelial activation. We hypothesize that alterations of microvascular cell surface markers likely mirror changes in the epicardial vessels that may be important in the pathophysiology of intimal proliferation.Forty-three heart transplant patients were examined by intracoronary ultrasound more than 1 year after transplantation, and these images were analyzed to obtain mean intimal thickness and intimal thickness class (I through IV), calculated from the mean thickness and circumferential involvement. Right ventricular endomyocardial biopsies obtained at the time of intracoronary ultrasound were examined by immunohistochemistry to detect microvascular expression of histocompatibility leukocyte antigen (HLA) classes I and II (HLA ABC, DR, DP, and DQ); endothelial-specific antigen detected by the monoclonal antibody E 1.5; intercellular adhesion molecules (ICAM-1); CD4+ and CD8+ lymphocytes and macrophages (CD 14+). Microvascular antigen expression was graded 1 through 5 on the basis of the diffuseness of positive staining. The number of each inflammatory cell phenotype present per high-power field was counted. By ANOVA, scores for HLA DR, HLA DQ, and E1.5 expression were lower in intimal thickness classes II, III, and IV compared with class I. This inverse relationship was significant by linear regression analysis of mean intimal thickness. Inflammatory cells were not significantly correlated with intimal thickening. Rejection incidence was higher, and time since transplantation longer, in intimal thickness classes II, III, and IV compared with class I.Transplant coronary artery intimal proliferation is associated with alteration of microvascular endothelial cell surface markers. These changes in cell surface antigen expression could provide the substrate for coronary artery intimal proliferation and narrowing.

    View details for Web of Science ID A1995QL45800006

    View details for PubMedID 7882470



    The purpose of this study was to quantify the severity of transplant coronary artery disease and to assess lesion characteristics early and up to 15 years after heart transplantation by using intracoronary ultrasound.Intravascular ultrasound has the ability to measure the components of the arterial wall and has been shown to be a sensitive method for detection of transplant coronary artery disease.A total of 304 intracoronary ultrasound studies were performed in 174 heart transplant recipients at baseline and up to 15 (mean 3.3 +/- 0.2) years after transplantation. Mean intimal thickness and an intimal index were calculated, and lesion characteristics (eccentricity, calcification) were assessed for all coronary sites imaged (mean 3.0 +/- 0.1 sites/study). The Stanford classification was used to grade lesion severity.Compared with findings in patients studied at baseline (< 2 months after transplantation, n = 50), mean intimal thickness (0.09 +/- 0.02 vs. 0.16 +/- 0.02 mm, p < 0.01), intimal index (0.07 +/- 0.01 vs. 0.14 +/- 0.02, p < 0.01) and mean severity class (1.5 +/- 0.2 vs. 2.3 +/- 0.2, p < 0.01) were significantly higher at year 1 (n = 52) after transplantation. Thereafter, all three variables further increased over time and reached highest values between years 5 and 15. Calcification of lesions was detected in 2% to 12% of studies up to 5 years after transplantation, with a significant increase to 24% at years 6 to 10 (p < 0.05).Severity of transplant coronary artery disease appeared to progress with time after transplantation in this cross-sectional study. This characteristic was most prominent during the 1st 2 years after transplantation, whereas calcification of plaques occurred to a significant extent only later in the process. These data may serve as a reference for comparison of intravascular ultrasound findings in other studies of patients with transplant coronary artery disease.

    View details for Web of Science ID A1995QL24900032

    View details for PubMedID 7798497



    We postulated that transplant coronary artery disease with rapid progression to more than 50% stenosis within a 1-year interval may have a different prognosis from transplant coronary artery disease with a more indolent rate of progression. Annual coronary angiograms of 139 consecutive patients who underwent transplantation between January 1968 and February 1990 who survived at least 1 year after transplantation and in whom angiographically apparent transplant coronary artery disease developed were included in the study. Of this group, 45 patients progressed from a normal angiogram to the presence of 50% or greater stenosis in one or more major vessels within 1 year (fulminant group); 94 did not (indolent group). Mean posttransplantation follow-up time was 5.3 +/- 4.1 years for patients with fulminant progression of disease and 6.6 +/- 3.7 years for those with indolent progression. A highly significant difference was found in the time-related incidence of ischemic events (myocardial infarction, congestive heart failure, sudden death, and retransplantation) between the indolent and the fulminant groups after initial detection of transplant coronary artery disease. At 1, 3, and 5 years after initial detection of transplant coronary artery disease, 50%, 33%, and 16% of patients in the fulminant group and 89%, 70%, and 60% of patients in the indolent group were free of ischemic events (p < 0.0001). The fulminant group of patients had a mean of 2.9 +/- 1.5 rejection episodes, and the indolent group a mean of 2.3 +/- 1.4 episodes (p = 0.02) during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994PV61100024

    View details for PubMedID 7865519

  • Recurrent lymphoma in a cardiac allograft recipient. Transplantation science Johnson, F., Hunt, S. 1994; 4 (1): 5-?

    View details for PubMedID 7804698

  • CARDIAC TRANSPLANTATION - THE STANFORD EXPERIENCE IN THE CYCLOSPORINE ERA JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Sarris, G. E., Moore, K. A., Schroeder, J. S., Hunt, S. A., Fowler, M. B., VALANTINE, H. B., Vagelos, R. H., Billingham, M. E., Oyer, P. E., Stinson, E. B., Reitz, B. A., Shumway, N. E. 1994; 108 (2): 240-252


    We analyzed our experience with 496 patients who underwent primary cardiac transplantation since the introduction of cyclosporine immunosuppression (Dec. 16, 1980, to Jan. 7, 1993). There were 388 male and 108 female patients. Mean recipient age was 40 +/- 16 years (range 0.1 to 70 years, median 44 years). Recipient diagnoses included coronary disease in 188, idiopathic cardiomyopathy in 196, viral cardiomyopathy in 35, and congenital heart disease in 28 patients. Donor age was 25 +/- 10 years (range 1 to 53 years, median 24 years). Graft ischemic time was 148 +/- 57 minutes (range 38 to 495 minutes, median 149 minutes). Operative mortality (hospital death) rate was 7.9% +/- 1.3% (70% confidence intervals). Multivariate logistic regression analysis revealed that (higher) pulmonary vascular resistance and gender (female) were the only independent predictors of hospital death (p < 0.05). Actuarial survival estimates for all patients at 1, 5, and 10 years are 82% +/- 1.7% (83% +/- 1.8% adult, 77% +/- 5.2% pediatric), 61% +/- 2.5% (65% +/- 2.5% adult, 64% +/- 6.6% pediatric), and 41% +/- 3.7% (40% +/- 4% adult, 54% +/- 8.6% pediatric), respectively. For 232 patients treated with triple-drug immunosuppression and induction with OKT3 since 1987, survival estimates at 1 and 5 years are 82% +/- 2.6% and 67% +/- 3.7%, respectively. Causes of death for the entire group were rejection in 29 (14% of deaths), infection in 69 (34%), graft coronary disease in 36 (18%), nonspecific graft failure in 6 (3%), malignancy in 19 (10%), stroke in 6 (3%), pulmonary hypertension in 6 (3%), and other causes in 30 (15%) patients. Actuarial freedom from rejection at 3 months, 1 year, and 5 years was 21% +/- 1.9%, 14% +/- 1.7%, and 7.2% +/- 1.5%, respectively (+/- 1 standard error of the mean). Estimates of freedom from rejection-related death at 1, 5, and 10 years were 96% +/- 1%, 93% +/- 1.4%, and 93% +/- 1.4%, respectively. Actuarial freedom from any infection at 3 months and at 1 and 5 years was 40% +/- 2.3%, 27% +/- 2.1%, and 15% +/- 2.0% and from infection-related death, 95% +/- 1.0%, 93% +/- 1.2%, and 85% +/- 1.9%, respectively. Actuarial freedom from (angiographic or autopsy proved) graft coronary artery disease at 1, 5, and 10 years was 95% +/- 1.2%, 73% +/- 2.7%, and 65% +/- 3.6% and from coronary disease-related death or retransplantation 98% +/- 0.7%, 84% +/- 2.2%, and 66% +/- 4.3%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for Web of Science ID A1994PB11400006

    View details for PubMedID 8041172



    Development of coronary artery disease (CAD) in the cardiac allograft limits long-term survival after heart transplantation. Previous studies, focusing on lipoprotein metabolism, have paid little attention to changes in glucose and insulin metabolism that increase the risk of CAD in these patients. To address this issue, plasma glucose and insulin responses to an oral glucose load and lipid and lipoprotein concentrations were measured in male normal volunteers (n = 40) and cardiac transplant recipients with pretransplant diagnoses of either idiopathic cardiomyopathy (n = 24) or ischemic heart disease (n = 28), matched for age and body mass index. Patients with a pretransplant diagnosis of ischemic heart disease had higher plasma glucose and insulin concentrations in response to oral glucose as well as higher fasting plasma triglyceride, cholesterol, and low-density lipoprotein cholesterol concentrations than did the control group (p < 0.005 to p < 0.001). In addition, high-density lipoprotein cholesterol concentrations were lower and the ratio of cholesterol to high-density lipoprotein cholesterol higher than control values in those with a pretransplant diagnosis of ischemic heart disease (p < 0.001). Values for almost all variables were intermediate in patients with a pretransplant diagnosis of idiopathic cardiomyopathy and in most instances were significantly different from both. Thus, male cardiac transplant recipients are dyslipidemic, relatively glucose intolerant, and hyperinsulinemic compared to normal volunteers. These changes, observed in patients with a pretransplant diagnosis of either ischemic heart disease or idiopathic cardiomyopathy, emphasize the important role of immunosuppression in the development of metabolic risk factors for CAD in these individuals.

    View details for Web of Science ID A1994NV84000010

    View details for PubMedID 8017286

  • LONG-TERM OUTCOME AFTER HEART-TRANSPLANTATION FOR PERIPARTUM CARDIOMYOPATHY AMERICAN HEART JOURNAL Rickenbacher, P. R., Rizeq, M. N., Hunt, S. A., Billingham, M. E., Fowler, M. B. 1994; 127 (5): 1318-1323


    To elucidate the long-term outcome and frequency of complications after heart transplantation for peripartum cardiomyopathy (PPCM), we compared the courses of eight consecutive patients undergoing transplantation for PPCM with those of nine female age-matched control subjects undergoing transplantation for idiopathic dilated cardiomyopathy (IDCM). No significant differences could be found in baseline variables between the two groups with the exception of the number of pregnancies (2.5 +/- 1.5 vs 0, p = 0.0002). Two patients in each group died during the first 6 months after transplantation, and one in each group died later. Actuarial survival rates were 75% +/- 15% and 78% +/- 14% (p = NS) at 1 year and 60% +/- 18% and 78% +/- 14% (p = NS) at 5 years in PPCM and IDCM patients, respectively. Linearized rejection rates during the first 3 months were 1.85 +/- 0.56 and 1.91 +/- 0.49 (p = NS) and during the second 3 months were 0.18 +/- 0.18 and 0.45 +/- 0.26 (p = NS), respectively. Similarly no significant differences in linearized infection rates were found. Among patients surviving more than 6 months after transplantation, after a mean follow-up period of 4.5 +/- 3.1 years for those with PPCM and 7.8 +/- 3.2 years for those with IDCM, 83% and 100%, respectively, were rehabilitated; hemodynamic findings were normal in all patients and the frequency of other transplant-associated complications was similar in both groups. In conclusion, heart transplantation is a valuable option for patients with PPCM and severe congestive heart failure that is unresponsive to conventional treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994NJ87900015

    View details for PubMedID 8172060



    Conflicting data exist on the role of graft rejection as a risk factor for later development of accelerated graft coronary artery disease. We analyzed 126 consecutive heart transplant recipients treated with cyclosporine-based immunosuppressive regimens and devised an arbitrary method to incorporate the number, duration, and severity of myocardial rejection episodes during the first postoperative year, resulting in a rejection score for each patient. We then correlated the later incidence (mean follow-up, 4 years) of angiographic accelerated graft coronary artery disease with this rejection score and with its components: number, duration, and severity of rejection; number and duration of untreated rejection; and incidence and duration of delayed rejection therapy. Accelerated graft coronary artery disease developed in 60 patients (48%). The rejection score was 96.7 for patients in the "no accelerated graft coronary artery disease" group and 110.4 for those in the "accelerated graft coronary artery disease" group (p = NS). No significant difference was noted between patients with and without disease in any of the other seven rejection parameters analyzed, and no significant difference in time to occurrence of disease was noted between groups divided at the median rejection score. Donor age was older and fasting triglyceride blood level was higher in patients with accelerated graft coronary artery disease than in those without disease. All other clinical characteristics, including HLA mismatches, ischemic time, blood pressure, lipid profile, and drug therapy, did not differ between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1993MP52100021

    View details for PubMedID 8312304



    Accelerated coronary artery disease is a major cause of late morbidity and mortality among heart-transplant recipients. Because calcium-channel blockers can suppress diet-induced atherosclerosis in laboratory animals, we assessed the efficacy of diltiazem in preventing coronary artery disease in transplanted hearts.Consecutive eligible cardiac-transplant recipients were randomly assigned to receive diltiazem (n = 52) or no calcium-channel blocker (n = 54). Coronary angiograms obtained early after cardiac transplantation and annually thereafter were used for the visual assessment of the extent of coronary artery disease. The average diameters of identical coronary artery segments were measured on the angiograms obtained at base line and at the first and second follow-up examinations.In the 57 patients who had all three angiograms, the average coronary artery diameter (+/- SD) 0.27 decreased in the group that received no calcium-channel blocker from 2.41 +/- 0.27 mm at base line to 2.19 +/- 0.28 mm at one year, and to 2.22 +/- 0.26 mm at two years (P < 0.001 for both years). The average diameter in the diltiazem group changed little from the base-line value of 2.32 +/- 0.22 mm (2.32 +/- 0.27 mm at one year and 2.36 +/- 0.22 mm at two years). The average change in the diameter of the segment differed significantly between the two treatment groups (P < 0.001), and the estimated effect of treatment changed only negligibly after adjustment for other relevant clinical variables. New angiographic evidence of coronary artery disease developed in 14 patients not given calcium-channel blockers, as compared with 5 diltiazem-treated patients (P = 0.082). Coronary stenoses greater than 50 percent of the luminal diameter developed in seven patients not given calcium-channel blockers, as compared with two patients given diltiazem; death due to coronary artery disease or retransplantation occurred in five patients in the group that did not receive calcium-channel blockers and none of those who received diltiazem.Our preliminary results suggest that diltiazem can prevent the usual reduction in the diameter of the coronary artery in cardiac-transplant recipients, but further follow-up will be required to determine whether diltiazem can decrease the long-term incidence of symptomatic coronary artery disease.

    View details for Web of Science ID A1993KG62500003

    View details for PubMedID 8417382

  • CARDIAC-FUNCTION AFTER DOMINO-DONOR HEART-TRANSPLANTATION AMERICAN JOURNAL OF CARDIOLOGY Kells, C. M., Marshall, S., Kramer, M., Hunt, S. A., Theodore, J., Valantine, H. A., Starnes, V. A. 1992; 69 (1): 113-116


    A major limitation in cardiac transplantation is donor availability. A possible way to increase the supply of donor hearts is to use explanted hearts from patients undergoing heart-lung transplantation for primary lung disease. One potential advantage of this approach, termed domino-donor transplantation, is the existence of a donor right ventricle already adapted to pulmonary hypertension, which would therefore theoretically decrease the likelihood of acute donor right heart failure in recipients with preexisting elevation of pulmonary vascular resistance. Potential disadvantages include graft failure secondary to chronic effects of pulmonary hypertension on the right ventricle, arrhythmia and infections. Seven domino-donor transplants were performed at Stanford University Hospital; graft and patient survival to date are 100% at a mean follow-up of 20 months (range 1 to 26). Infection and rejection rates have been comparable to those of the current Stanford experience for conventional orthotopic transplantation. Right ventricular function and size have either improved or remained unchanged in all patients after transplantation. Transient early postoperative donor right ventricular dilation, a characteristic adaptive response seen in nondomino transplants, occurred in 4 patients with pulmonary hypertension before surgery. These data indicate that, with adequate assessment before surgery, domino-donor cardiac transplantation is an appropriate means of augmenting the donor pool.

    View details for Web of Science ID A1992GY22500019

    View details for PubMedID 1729859



    Coadministration of diltiazem with cyclosporine (CsA) has been reported to alter the metabolism of CsA, resulting in increased blood concentration with potential nephrotoxicity if dosage is not adjusted. This report analyzes the cost saving resulting from use of diltiazem and CsA together and examines the impact on renal function. Sixty-nine heart transplant recipients (59 men, 10 women) were randomized to diltiazem (n = 32) or to no calcium blocker (n = 37). Age range was 18 to 58 years. All patients received CsA (titrated to a 12-hour trough serum level of 100 to 200 ng/ml), azathioprine, and prednisone. Diltiazem was begun at 30 mg three times daily increasing to 60 mg three times daily at 1 month, as tolerated. Renal function was assessed by serial measurements of serum creatinine. Parameters before and after starting diltiazem were compared by paired t-tests, and differences between group means by analysis of variance. CsA doses and levels were comparable at baseline in both groups. At 12 months, CsA dose requirement was 2.5 +/- 1.0 versus 5.9 +/- 3.2 mg/kg/day (diltiazem group versus no calcium blocker group; p less than or equal to 0.001) to achieve similar serum levels (96 +/- 51 versus 123 +/- 96 ng/ml; p = NS). This represents a 48% reduction in dose cost of CsA. The average cost of CsA for 2 to 4 months of therapy in a patient weighing 70 kg was reduced from $12,122 in the no calcium blocker group to $6,356 in the diltiazem group.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1992HC24900001

    View details for PubMedID 1540597



    To characterize "normal electrocardiogram patterns" after transplantation, serial surface 12-lead electrocardiograms (ECGs) taken 2 weeks, 1 month, and 1 year postoperatively in a group of 50 heart transplant recipients were analyzed and were correlated with clinical parameters. Some recipient atrial activity was evident in 40% of patients at 2 weeks, but in only 16% at 1 year; donor atrial activity was normal in 90% to 94% of patients at all times. ECG intervals generally were normal and did not change over time. The most prevalent abnormality was the presence of incomplete (IRBBB) or complete right bundle branch block (RBBB) patterns (14% at 2 weeks, 16% at 1 month, and 22% at 1 year). In patients with hemodynamic measurements available approximately at the time of the ECG recording 1 year following transplantation, there was a significant correlation between the presence of IRBBB and RBBB patterns and somewhat higher levels of right atrial mean pressure (6.8 versus 3.9 mm Hg, p = 0.01), pulmonary artery systolic pressure (32.5 versus 24.5 mm Hg, p = 0.001) and diastolic pressure (16.2 versus 11.2 mm Hg, p = 0.004), and right ventricular systolic pressure (31.4 versus 26.9 mm Hg, p = 0.019) and pulmonary artery wedge mean pressure (11.3 versus 7.9 mm Hg, p = 0.010). Repolarization changes were also common but decreased in frequency over time (78% at 2 weeks to 34% at 1 year) and did not correlate with the presence or absence of rejection. We conclude that ECG abnormalities in heart transplant recipients are generally mild and that IRBBB and RBBB patterns correlate with increased right heart pressures.

    View details for Web of Science ID A1991GD34100023

    View details for PubMedID 1877454



    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for "salvage" therapy of cardiac allograft rejection unresponsive to conventional therapy.

    View details for Web of Science ID A1991FE16600002

    View details for PubMedID 2031918



    Accelerated coronary artery disease is a major cause of morbidity and mortality among cardiac transplant recipients. Ten patients who died or underwent retransplantation within 2 months of coronary angiography had direct correlation of angiographic (normal discrete lesions, diffuse concentric narrowing) with histologic appearance of coronary arteries. Of the 26 angiographically normal segments, 73% showed mild to moderate fibrous intimal thickening by light microscopy. The remainder had intermediate lesions or atheromatous plaques. Discrete stenoses usually corresponded to lipid-rich intermediate or atheromatous disease. In contrast, angiographically diffuse, concentrically narrowed lesions usually were areas of severe fibrous intimal thickening. Fresh or organizing thrombus was most often associated with discrete lesions and accounted for all complete occlusions. Histologic and angiographic comparisons of the degree of luminal narrowing showed generally good correlation for high grade stenoses. Lesions graded as having less than 25% diameter narrowing were often underestimated angiographically as compared with histologic determinations. Transplant coronary artery disease has a heterogeneous histologic and angiographic appearance, with angiographic underestimation of disease in some patients.

    View details for Web of Science ID A1991EY08300025

    View details for PubMedID 1991903



    Over 12,000 cardiac transplants have been performed worldwide and many recipients are alive between 10 and 20 years posttransplant. The results, complications, and pathology of the long-term survivors are discussed in this chapter.

    View details for Web of Science ID A1991FE08600041

    View details for PubMedID 1827971



    Increased rejection incidence in female heart transplant recipients receiving immunosuppressive therapy with cyclosporine and azathioprine has been reported and a possible role for gender-mismatched grafting (male donor into female recipient) has been suggested. To test the hypothesis that rejection is more frequent in female patients receiving male hearts, we analyzed the results of heart transplantation in gender-matched and -mismatched grafts in 313 recipients maintained with either double therapy with cyclosporine and prednisone (group 1, n = 104) or triple therapy with cyclosporine, azathioprine, and prednisone (group 2, n = 209). There were 21 female recipients in group 1 and 41 in group 2. The variables studied were 90-day total methylprednisolone sodium succinate requirements, 90-day linearized rejection rate, 90-day event-free actuarial rejection, 6-month actuarial infection-free survival, overall actuarial survival, and median day to first rejection. Statistical analyses included two-tailed t or Cox-Mantel testing as appropriate. In group 1, transplantation of a male heart into a female recipient (M/F grafting) was associated with a 40% higher 90-day cumulative steroid requirement (5008 +/- 3400 mg for M/F vs 3600 +/- 2977 mg for F/F), reflecting a higher rate of rejection in M/F recipients. Linearized rejection rates (90-day) were higher (1.6 +/- 0.4 vs 1.3 +/- 0.5 episodes per patient), and consequent 6-month event-free infection rates were lowest in these patients, although not significantly so. Actuarial survival did not differ significantly between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1991EZ48400016

    View details for PubMedID 2007161

  • Progressive coronary luminal narrowing after cardiac transplantation. Circulation Gao, S. Z., Alderman, E. L., Schroeder, J. S., Hunt, S. A., WIEDERHOLD, V., Stinson, E. B. 1990; 82 (5): IV269-75


    Accelerated coronary disease is a major factor limiting long-term survival in cardiac transplant recipients. Coronary angiography was obtained a mean of 5.1 weeks posttransplantation and annually thereafter. Replicate projections recorded after nitroglycerine administration were quantitated using computer-assisted edge detection. Five hundred and fifteen coronary segments in 25 patients having 1-year follow-up and 353 segments in 18 patients reaching 2-year follow-up were compared with baseline angiograms. Significant change was defined as +/- 0.10 mm, equal to 3.8% change in diameter based on three standard deviations obtained from estimation of measurement error. Mean coronary diameter fell from 2.44 +/- 0.26 mm at baseline to 2.21 +/- 0.34 mm (p less than 0.001) at 1-year follow-up. This rate of diameter decline was 20-fold more rapid during the initial posttransplantation year than the rate of change of visually normal segments in nontransplant patients with coronary atherosclerosis elsewhere. There was no significant drop in mean diameter between the first and second year in those patients who had second-year studies. Decrease in absolute diameter for vessels greater than 2.9 mm significantly exceeded diameter reduction for smaller vessels but did not differ when considered as a ratio of vessel diameter. In 21 of 25 patients, mean coronary diameter reduction exceeded the three-standard deviation threshold at their last angiogram, but only two of these patients had visually detectable transplant coronary disease.

    View details for PubMedID 2225415

  • Accelerated transplant coronary artery disease. Seminars in thoracic and cardiovascular surgery Gao, S. Z., Hunt, S. A., Schroeder, J. S. 1990; 2 (3): 241-249

    View details for PubMedID 1964396



    We present cardiac and pulmonary function data obtained at serial annual reviews in 21 heart-lung transplant (HLT) recipients followed for up to four years postoperatively, reflecting the entire Stanford experience as of June 1987. A total of 50 cardiac catheterisation procedures and endomyocardial biopsies yielded the following results: rejection on biopsy (0/50) (0% of patients), angiographic coronary artery disease (1/50) (5%), pulmonary hypertension (2/50) (10%), elevated pulmonary vascular resistance (PVR) (1/50) (5%), and low cardiac index (CI) (4/50) (14%). Systemic hypertension was common, with an elevated systemic vascular resistance (SVR) (26/44) (76%) and an elevated mean aortic pressure (MAP) (22/44) (67%). Pulmonary function testing frequently revealed abnormalities. Airflow limitation was manifested by a reduction in both FEV1/FVC ratio (17/50) (52%) and FEF25-75 (30/50) (71%), and was often associated with arterial hypoxaemia (13/50) (52%). Subsequently, five patients with these findings have died with obliterative bronchiolitis (OB), one underwent retransplantation for OB, six have stable OB, and one has progressive OB. Length of survival was highly correlated with the resting PaO2 at the first annual review (r = 0.99) (p less than 0.001), and, to a lesser degree, on the reduction in FEF25-75 (r = 0.73) (p less than 0.05) and FEV1/FVC ratio (r = 0.77) (p less than 0.05). Resting PaO2 was determined by ventilatory (r = 0.80) (p less than 0.001) rather than circulatory factors and all patients with airflow limitation who died had OB at post-mortem examination. These results support the continued study of HLT as a therapeutic modality for selected patients with irreversible pulmonary hypertension. They demonstrate that, in the absence of severe OB, haemodynamics, cardiac function, and coronary patency are preserved for several years after HLT. Whereas the value of regular pulmonary function testing has become evident, there does not appear to be a clinical need for annual surveillance with invasive cardiac procedures in long-term survivors of HLT.

    View details for Web of Science ID A1990DL20800004

    View details for PubMedID 2372269

  • CARDIAC TRANSPLANTATION IN PATIENTS WITH PREEXISTING NEOPLASTIC DISEASES AMERICAN JOURNAL OF CARDIOLOGY Edwards, B. S., Hunt, S. A., Fowler, M. B., Valantine, H. A., Stinson, E. B., Schroeder, J. S. 1990; 65 (7): 501-504


    Cardiac transplantation has traditionally been reserved for individuals with end-stage congestive heart failure (CHF) in whom there is no history of other life-threatening systemic disorders. In most transplant centers, patients with a history of malignancy and severe heart failure have not been considered acceptable candidates for cardiac transplantation. In the last 4 years at Stanford University Medical Center, 8 cardiac transplants have been performed in 7 patients with a history of neoplastic disease. Six of these patients had already received treatment for lymphoproliferative disorders and in 1 case, a patient underwent a transplant after treatment for adenocarcinoma of the colon. Six of the 7 patients were discharged from the hospital and in that group, the 1-year posttransplant survival rate was 71%. This was comparable to an overall 1-year survival rate of 80% for patients undergoing a cardiac transplant at our center during the same period of time. At follow-up averaging over 2 years, there has been 1 case of recurrent neoplasia. One patient with evidence of radiation-induced pulmonary damage died of respiratory failure 2 days after transplantation. One patient required retransplantation because of intractable rejection and subsequently died from infectious complications. Immunosuppressive therapy in these patients has not been associated with an increased risk for neoplastic recurrence or for the development of posttransplant lymphoproliferative disorders. The current study demonstrates that in a carefully selected group, previously treated neoplastic disease should not represent a contraindication to cardiac transplantation.

    View details for Web of Science ID A1990CN83200019

    View details for PubMedID 2305689

  • ACUTE MYOCARDIAL-INFARCTION IN CARDIAC TRANSPLANT RECIPIENTS AMERICAN JOURNAL OF CARDIOLOGY Gao, S. Z., Schroeder, J. S., Hunt, S. A., Billingham, M. E., Valantine, H. A., Stinson, E. B. 1989; 64 (18): 1093-1097


    To characterize the clinical and pathologic features of acute myocardial infarction (AMI) in cardiac transplant recipients, 22 Stanford patients who had 25 documented infarcts at a mean of 3.86 years after transplantation were reviewed. Symptoms included chest pain (2), arm pain (3), weakness (16), dyspnea (11) and palpitations (8). Three episodes were clinically silent, detected only as new electrocardiographic changes during routine follow-up. Of 18 patients hospitalized with symptoms, only 7 had electrocardiographic changes of typical Q-wave AMI; 5 had nonspecific ST-segment changes and 2 had no documented changes. Two had old Q waves. Twelve of the 18 were misdiagnosed at admission as having infection or congestive heart failure. Serial creatine phosphokinase levels were obtained in 13 patients, and values were elevated in 8. Six of 25 AMI episodes were associated with development of congestive heart failure and 4 others led to development of cardiogenic shock. Seven patients died during the acute phase of infarction, 12 were retransplanted from 2 days to 6 months after infarct and 1 died suddenly after discharge. Two healed myocardial infarctions of unknown duration were found at autopsy or on explantation in patients not clinically suspected of having an AMI. All infarcts occurred in patients known to have angiographic evidence of transplant coronary artery disease, based on annual coronary arteriography. At autopsy or explantation all hearts were found to have characteristic diffuse concentric coronary artery narrowing, and 4 (18%) had an unusual pattern of multiple foci of nontransmural AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1989AZ54800002

    View details for PubMedID 2816760

  • Prevalence of accelerated coronary artery disease in heart transplant survivors. Comparison of cyclosporine and azathioprine regimens. Circulation Gao, S. Z., Schroeder, J. S., Alderman, E. L., Hunt, S. A., Valantine, H. A., WIEDERHOLD, V., Stinson, E. B. 1989; 80 (5): III100-5


    Rapid development of diffuse, occlusive coronary artery disease in the cardiac allograft has emerged as a major limiting factor for long-term survival after transplantation. Prior multivariate analyses have failed to identify any strong predictors of this disease. We retrospectively reviewed serial annual coronary angiograms to assess the prevalence of transplant coronary artery disease. A total of 103 patients treated initially with azathioprine-based therapy were compared with a later cohort of 78 patients for whom cyclosporine was the basis of immunosuppressive therapy. The percent of patients free of angiographically visible transplant coronary artery disease at 1 year was 89% for the azathioprine group versus 86% for the cyclosporine group. At 3 years, 74% of the azathioprine group versus 63% of the cyclosporine group were free of visible disease (p = NS). By the fifth postoperative year, 58% of azathioprine-treated and 50% of cyclosporine-treated patients were free of transplant coronary artery disease (p = NS). The mean number of rejection episodes in the first year after transplantation was 2.0 for cyclosporine patients versus 2.5 for azathioprine patients. The azathioprine and cyclosporine patients were compared with respect to a variety of baseline and clinical follow-up measurements that might influence the development of coronary artery disease. Patients in the cyclosporine group had higher blood pressure (135/94 versus 123/85 mm Hg, p less than 0.001) and were receiving lower maintenance prednisone doses. This study demonstrates that improved cyclosporine immunosuppression does not decrease the time-related prevalence of transplant coronary artery disease.

    View details for PubMedID 2805287



    A familial etiology was identified on the basis of family history in 16 (8.75%) of 184 patients undergoing cardiac transplantation at Stanford for endstage dilated cardiomyopathy (DC). These 16 patients, from 11 families, included 5 sibling pairs. To help determine optimal management of such patients, their case histories and posttransplant courses were reviewed. Mean age of patients at presentation was 23 +/- 15 years. In sibling pairs, duration of symptoms from onset to diagnosis was 14 +/- 5 weeks for the first sibling, but only 4 +/- 2 weeks for the second. Progressive cardiac enlargement was documented radiographically in siblings of transplant recipients in 2 families before the onset of symptoms. The posttransplant course with regard to rejection incidence, infectious complications, coronary artery disease and malignancy was similar to that of the 168 patients with nonfamilial DC. Actuarial survival at 5 years after transplantation was 80%. Thirteen patients (including all sibling pairs) are alive 1 to 11 years after transplantation. Sepsis was the cause of death in 3 patients, occurring during the early postoperative period in 2 and following retransplantation for graft atherosclerosis 7 years after the initial transplant in the third patient. Thus, diagnosis of DC in childhood or adolescence mandates evaluation and surveillance of family members, because this disease can progress rapidly. The favorable results of cardiac transplantation for familial DC suggest that it should be promptly considered for such patients with end-stage disease.

    View details for Web of Science ID A1989U107900014

    View details for PubMedID 2648793

  • INCREASING PERICARDIAL-EFFUSION IN CARDIAC TRANSPLANT RECIPIENTS CIRCULATION Valantine, H. A., Hunt, S. A., Gibbons, R., Billingham, M. E., Stinson, E. B., Popp, R. L. 1989; 79 (3): 603-609


    Although pericardial effusion after cardiac surgery is frequent and usually benign, its etiology and prognosis after cardiac transplantation are unknown. During 1 year (1985-1986), 12 of our current transplant population (total, 189) developed moderate or large pericardial effusions confirmed by two-dimensional echocardiography. These effusions occurred within 1 month of transplantation in 10 patients and at 3 months and 4.5 years in the other two. Pericardiocentesis was performed because of clinical evidence of increasing effusions in eight patients, with demonstrable hemodynamic compromise secondary to tamponade in five. Pericardial fluid was sterile in all but one. Endomyocardial biopsy at the time of increasing effusion revealed moderate acute rejection in five patients, mild rejection in three, and no rejection in four. All three patients with mild rejection had moderate acute rejection on subsequent biopsy performed within 7 days. In two of the four with no rejection, repeat biopsy within 5 days showed moderate acute rejection; in a third, moderate rejection was present on biopsy performed 14 days later. Legionella dumoffii was isolated from the pericardial fluid of the fourth patient, whose subsequent biopsies never showed rejection. Three of the 12 patients developed progressive ventricular dysfunction sufficiently severe to require retransplantation. One patient died suddenly 12 months after transplantation, and autopsy examination revealed severe coronary artery disease. Two died of sepsis within 3 months of transplantation. Intense inflammatory infiltrates and thickening of the pericardium and epicardium were characteristically present in explanted and autopsy hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1989T597000015

    View details for PubMedID 2645065



    Conventional hemodynamic measurements and Doppler echocardiography were used to assess ventricular physiology of the human cardiac allograft and to examine the influence of pertinent clinical factors on chronic myocardial performance. Sixty-four patients (18-55 years old; mean, 39 years) undergoing routine annual hemodynamic assessment were studied. Blood-flow velocity properties across the mitral, tricuspid, and aortic valves were analyzed from Doppler ultrasound recordings. Ten of these patients had elevated diastolic pressures associated with a sharp early diastolic dip followed by an exaggerated and abrupt rise in pressure, consistent with restrictive-constrictive ventricular physiology. Left ventricular dP/dt and stroke volume were lower in these patients compared with the other 54 patients. Doppler echocardiographic indexes of left ventricular filling and ejection in these 10 patients differed significantly. Isovolumic relaxation time and pressure half-time were shorter, peak early mitral and tricuspid flow velocities were higher, and mean aortic flow velocity and acceleration were lower. A higher rejection incidence was the only demonstrable clinical factor associated with impaired ventricular function. Doppler echocardiography may, therefore, noninvasively identify patients with hemodynamic evidence of restrictive-constrictive physiology. This abnormality occurs in approximately 15% of allograft recipients, is associated with impaired systolic performance, and may be related to rejection incidence.

    View details for Web of Science ID A1989R718300009

    View details for PubMedID 2642757



    Development of accelerated coronary artery disease (CAD) in the cardiac allograft is one of the major causes of late graft failure in heart transplant recipients. At the Stanford University Medical Center 356 heart transplant procedures were performed in 329 patients by the end of January 1985. Eighty-nine of these patients developed evidence of transplant CAD. Twenty retransplant procedures, including 2 third transplants, were performed in 19 of the 89 patients because of transplant CAD. The graft survival rates after the second transplant were 55%, 25% and 10% after 1, 2 and 5 years, respectively. Nine of these retransplant patients currently survive, the longest for 5.5 years. To examine potential risk factors for development of severe transplant CAD, these 20 retransplant procedures were compared with 113 transplant recipients who had no evidence of transplant CAD on annual coronary arteriograms. An excess of rejection episodes (3 +/- 2 vs 2 +/- 1 episodes/patient, p = 0.02), elevated total cholesterol (266 +/- 78 vs 225 +/- 47 mg/dl, p = 0.002) and higher low-density lipoprotein levels (176 +/- 88 vs 137 +/- 46 mg/dl, p = 0.009) were noted in the transplant CAD retransplant group. Five of 11 retransplant recipients who survived greater than 1 year again developed transplant CAD. Characteristic morphologic features and rapid progression of CAD in the second graft were similar to those in the primary graft.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1988Q603600006

    View details for PubMedID 3052011



    Annual coronary arteriograms have been obtained from all heart transplant recipients at Stanford University Medical Center since 1969. Angiographic lesions in 81 transplant patients exhibiting coronary vascular disease were classified into three categories: type A, discrete or tubular stenoses; type B, diffuse concentric narrowing; and type C, narrowed irregular vessels with occluded branches. The 81 arteriograms showing transplant coronary vascular disease were contrasted with 32 from nontransplant patients with coronary artery disease analyzed in a similar fashion. The nontransplant angiograms showed 178 lesions, all of type A (discrete or tubular) morphology, 75% of which were located in primary epicardial coronary vessels and 25% in secondary branch vessels. In the patients with transplant coronary vascular disease, 349 (76%) of 461 lesions were type A: 57% in primary vessels, 42% in secondary branches and 1.4% in tertiary branches. Of the 112 type B and C lesions (diffuse narrowing, tapering and obliteration), 25% were in primary vessels, 44% in secondary vessels and 31% in tertiary branches (p less than 0.05 for patients with transplant coronary vascular disease versus patients with nontransplant coronary artery disease). Total vessel occlusion was found in proximal or middle vessel segments in 96% and distally in 4% of patients with "ordinary" coronary artery disease versus 49% distally in patients with transplant coronary disease (p less than 0.002). In the presence of total vessel occlusion, collateral vessels were poor or absent in 92% of transplant versus 7% of nontransplant patients with coronary disease (p less than 0.002). Therefore, coronary artery disease in transplant patients represents a mixture of typical atheromatous lesions and unique transplant-related progressive distal obliterative disease that occurs without collateral vessel development.

    View details for Web of Science ID A1988P527800006

    View details for PubMedID 3292629



    The contribution of the donor heart to total circulatory performance after heterotopic heart transplantation has been difficult to assess. First-pass nuclear angiocardiography and directional Doppler echocardiography were used to examine separately left and right ventricular function of the donor heart after heterotopic transplantation. A comparison was made between two patients, one with a low initial pulmonary vascular resistance and one with a high, relatively fixed pulmonary vascular resistance. In both cases, currently available noninvasive techniques allowed confirmation of the expectation that the donor left ventricle can function effectively as a left ventricular bypass. In neither case was recovery of the native heart demonstrated. The contribution of the donor right ventricle to total right ventricular output appeared to be dependent on the condition of the donor heart and on the pulmonary vascular resistance. In situations with a high pulmonary vascular resistance and end-stage right ventricular failure, it was concluded that the donor heart may not at first constitute an effective assist for the native right ventricle. Native right ventricular failure may then become a major factor influencing survival after heterotopic heart transplantation.

    View details for Web of Science ID A1988L686700010

    View details for PubMedID 3275840


    View details for Web of Science ID A1987L039900026

    View details for PubMedID 3312688

  • CARDIAC TRANSPLANTATION IN CHILDREN AND ADOLESCENTS CIRCULATION Starnes, V. A., Stinson, E. B., Oyer, P. E., Valantine, H., Baldwin, J. C., Hunt, S. A., Shumway, N. E. 1987; 76 (5): 43-49
  • Clinical and laboratory correlates of accelerated coronary artery disease in the cardiac transplant patient. Circulation Gao, S. Z., Schroeder, J. S., Alderman, E. L., Hunt, S. A., Silverman, J. F., WIEDERHOLD, V., Stinson, E. B. 1987; 76 (5): V56-61


    Accelerated coronary disease in the cardiac allograft (TxCAD) is a major complication affecting long-term survival of heart transplant patients. Since the transplanted heart remains denervated, the first sign of TxCAD may be silent myocardial infarction or sudden death. The prevalence of this disease has been unaltered since the advent of cyclosporine immunosuppression. Serial annual coronary arteriograms in 132 patients undergoing transplantation after 1979 at Stanford revealed 44 patients who developed TxCAD (33%). Multiple variables, including patient lipid profile, extent of donor and recipient tissue match, age of recipient and donor, number of rejection episodes, prednisone dose, and fasting blood sugar were examined in relation to occurrence of TxCAD. Donor age was greater among the 44 patients developing TxCAD that in the 88 patients who did not develop coronary artery disease (23.5 +/- 5.8 vs 21.3 +/- 5.7 years, p less than .05). The fasting plasma triglyceride level 1 year after transplantation was 236.0 +/- 246.3 mg% in the patients with TxCAD vs 170.1 +/- 108.2 mg% in those without TxCAD (p less than .05). No other indexes, including number of rejection episodes during first posttransplant year, number of HL-A mismatches, level of maintenance steroids, fasting blood sugar, and cholesterol subfractions identified patients who developed TxCAD. We conclude that TxCAD has limited correlation with the clinical and laboratory factors analyzed. Higher donor age and elevated plasma triglycerides may be significant predisposing factors for the development of TxCAD.

    View details for PubMedID 3311457

  • Changes in Doppler echocardiographic indexes of left ventricular function as potential markers of acute cardiac rejection. Circulation Valantine, H. A., Fowler, M. B., Hunt, S. A., NAASZ, C., Hatle, L. K., Billingham, M. E., Stinson, E. B., Popp, R. L. 1987; 76 (5): V86-92


    Changes in left ventricular filling and ejection as potential markers of cardiac allograft rejection were evaluated by serial Doppler echocardiography performed in 23 normal volunteers and within 24 hr of endomyocardial biopsy in 22 patients aged 14 to 53 years (mean 37). Peak aortic velocity, left ventricular ejection time index (ETI), isovolumic relaxation time (IVRT), mitral valve pressure half-time (PHT), peak early mitral flow velocity (M1), and velocity following donor atrial systole (M2) were measured without prior knowledge of endomyocardial biopsy findings. Biopsy specimens were graded histologically as: no rejection, mild rejection (cellular infiltrate), and moderate rejection (myocyte necrosis). A total of 120 biopsy-correlated Doppler echocardiographic studies were performed during 16 weeks after cardiac transplantation. Heart rate and mean arterial pressure were significantly higher in transplant recipients than in normal subjects. IVRT and PHT were significantly longer, while M1 and M2 were similar. Peak aortic velocity was higher in normal subjects than in transplant recipients, while ejection time was similar. Rejection of increasing severity was associated with a progressive shortening of IVRT and PHT and with an increase in M1 (p less than .0005 for all comparisons). Peak aortic velocity and ejection time index did not change significantly with rejection. These data indicate that acute cardiac rejection is accompanied by alteration in left ventricular filling dynamics detectable by Doppler echocardiography, without measureable changes in systolic function. These changes may provide noninvasive markers for surveillance of rejection.

    View details for PubMedID 3311461

  • Cardiac transplantation in children and adolescents. Circulation Starnes, V. A., Stinson, E. B., Oyer, P. E., Valantine, H., Baldwin, J. C., Hunt, S. A., Shumway, N. E. 1987; 76 (5): V43-7


    Cardiac transplantation represents an expanding therapeutic modality for end-stage heart disease in children and adolescents. During the past 5 years, 27 patients (15 boys; 12 girls) between the ages of 2 and 18 have undergone cardiac transplantation. The preoperative diagnosis was cardiomyopathy in 24 (six familial), congenital heart disease in two, and endocardial fibroelastosis in one. Immunosuppression included cyclosporine, azathioprine, and prednisone. There were 22 survivors, with four hospital deaths (three infection, one pulmonary hypertension), and one death at 4.5 years from graft atherosclerosis. The actuarial survival at 4 years was 83 +/- 7.4% and that at 5 years was 69 +/- 14.2%. Renal function was stable at 4 years, with an average creatinine clearance of 69.75 +/- 27.0 ml/min/m2. Hypertension was present in 21 of 22 patients, who require multiple drug therapy. Rehabilitation is 100% among discharged patients, with 14 in school, six employed, and two toddlers.

    View details for PubMedID 3311454

  • Cardiac sarcoidosis: response to steroids and transplantation. journal of heart transplantation Valantine, H. A., Tazelaar, H. D., Macoviak, J., MULLIN, A. V., Hunt, S. A., Fowler, M. B., Billingham, M. E., Schroeder, J. S. 1987; 6 (4): 244-250


    From 1976 to 1986, six cases of cardiac sarcoidosis have been documented by myocardial biopsy in three of five instances; on examination of the explanted heart after transplantation in two, and at autopsy in one patient. Right ventricular end-diastolic pressure was elevated in all four patients with right ventricular involvement with sarcoidosis. Of three patients treated with steroids, improvement in ventricular function and decrease in arrhythmia occurred in two, whereas failure to respond led to transplantation in the other patient. Two further patients have undergone heart transplantation, one for resistant ventricular arrhythmia and the other for congestive heart failure. No recurrence of sarcoidosis has occurred in the grafts. Because two of five patients had sarcoidosis diagnosed on gross examination, a negative endomyocardial biopsy does not exclude the diagnosis of myocardial sarcoidosis, which should therefore be pursued in the setting of unexplained heart failure, conduction abnormalities, and ventricular arrhythmia, particularly when right ventricular end-diastolic pressure is raised. Steroids may result in improvement in some patients even in the presence of severe morphological damage. Heart transplantation may be performed without increased risk of recurrence of sarcoidosis.

    View details for PubMedID 3312535



    Recipient atrial remnants retain electrical and mechanical activity after orthotopic cardiac transplantation. This study investigated the influence of recipient atrial contraction timing on Doppler ultrasound mitral flow velocity curves, isovolumic relaxation time, peak early mitral flow velocity (M1), mitral valve pressure half-time and peak mitral flow velocity due to atrial systole (M2). Clearly identifiable recipient atrial electrical activity (P waves) was present in 7 of 10 patients studied early postoperatively 2 to 6 months (mean 2.5) (early group) and in 20 of 24 patients seen 1 to 11 years (mean 3) after transplantation (late group). Median age and gender distribution were similar in both groups. For analysis of its influence on isovolumic relaxation time, pressure half-time and M1, recipient atrial contraction was classified by its position in the cardiac cycle as early systole, late systole or diastole. For analysis of M2, it was classified as early diastole, late diastole or systole. Compared with its occurrence in diastole, recipient atrial contraction in late systole was associated with a shorter isovolumic relaxation time, shorter pressure half-time and higher M1. In early systole it was associated with a longer pressure half-time and lower M1 than in diastole; isovolumic relaxation time was unchanged. Recipient atrial contraction in early diastole resulted in a lower M2 than in systole, whereas simultaneous contraction of recipient and donor atria in late diastole resulted in an increase in M2. These results indicate that the timing of recipient atrial contraction and relaxation significantly influences left ventricular filling dynamics.

    View details for Web of Science ID A1987H365700028

    View details for PubMedID 3554953

  • HYPOXIC PULMONARY VASOCONSTRICTION PERSISTS IN THE HUMAN TRANSPLANTED LUNG CLINICAL SCIENCE Robin, E. D., Theodore, J., Burke, C. M., Oesterle, S. N., Fowler, M. B., Jamieson, S. W., Baldwin, J. C., Morris, A. J., Hunt, S. A., VANKESSEL, A., Stinson, E. B., Shumway, N. E. 1987; 72 (3): 283-287


    The preservation of hypoxic pulmonary vasoconstriction (HPV) in the denervated lung was studied in five human heart-lung transplant recipients. All five patients showed significant increases in mean pulmonary artery pressure and pulmonary vascular resistance during hypoxic exposure, returning toward normoxic values during recovery. Aside from PAO2 and Pao2, other factors known to influence pulmonary vascular resistance did not change significantly during the hypoxic period. There was no relation between the length of the post-transplantation period and the intensity of HPV, suggesting that reinnervation of the pulmonary vascular bed did not account for persistent HPV and that HPV persists in the human transplanted lung despite the loss of autonomic neural innervation.

    View details for Web of Science ID A1987G007200004

    View details for PubMedID 3545645


    View details for Web of Science ID A1987G101500252

    View details for PubMedID 3274554


    View details for Web of Science ID A1987G101500265

    View details for PubMedID 3547937

  • COMBINED HEART-LUNG TRANSPLANTATION FOR END-STAGE EISENMENGERS SYNDROME JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY McGregor, C. G., Jamieson, S. W., Baldwin, J. C., Burke, C. M., Dawkins, K. D., Stinson, E. B., Oyer, P. E., Billingham, M. E., Zusman, D. R., Reitz, B. A., Yousem, S., Hunt, S. A., Shumway, N. E. 1986; 91 (3): 443-450


    Between May, 1981, and December, 1984, thirteen combined heart-lung transplants were performed in 12 patients for the treatment of Eisenmenger's syndrome. The age range of the recipients was 22 to 42 years. Two patients had undergone previous open cardiac operations; in addition, one had had closure of a persistent ductus arteriosus, one an open lung biopsy, one a pulmonary artery banding, and one patient received a second heart-lung transplant after 3 years. Four recipients died before hospital discharge, one at operation and three at 4, 10, and 33 days after operation. Early symptomatic results and cardiopulmonary function were excellent in all of the survivors. Two patients died 14 and 15 months after transplantation of accelerated graft arteriosclerosis and respiratory failure, respectively, and six remain alive 7 to 44 months after transplantation. Four of these surviving patients and the two patients who died late subsequently had major pulmonary complications. Symptoms included progressive breathlessness, cough (often productive), and fever with physical signs of diffuse crepitations and expiratory rhonchi. Serial pulmonary function tests showed progressive obstructive physiology in all six patients with superimposed restrictive defects in four. Histologic examination of tissue from open lung biopsy or autopsy displayed bronchiolitis obliterans in five of these patients, one of whom required retransplantation. It is possible that these late changes are the result of rejection, since similar changes in one other patient have now been reversed with augmented immunosuppression. Further understanding of the causes and manifestations of late pulmonary deterioration should improve the late functional results of this operation for Eisenmenger's syndrome.

    View details for Web of Science ID A1986A435500016

    View details for PubMedID 3081765

  • LATE RESULTS OF COMBINED HEART LUNG TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Jamieson, S. W., Dawkins, K. D., Burke, C., Baldwin, J. W., YOUSEUR, S., Billingham, M. E., Hunt, S. A., Reitz, B. A., Theodore, J., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 17 (1): 212-214
  • LONG-TERM RESULTS, HEMODYNAMICS, AND COMPLICATIONS AFTER COMBINED HEART AND LUNG TRANSPLANTATION CIRCULATION Dawkins, K. D., Jamieson, S. W., Hunt, S. A., Baldwin, J. C., Burke, C. M., Morris, A., Billingham, M. E., Theodore, J., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 71 (5): 919-926


    During the first 31/2 years of the Stanford heart-lung transplant program, 23 transplants have been carried out in 22 patients with severe pulmonary vascular disease. Actuarial survival curves predict 1 and 2 year survival rates of 71% and 57%, respectively, for all patients. As a result of increasing experience, the early mortality of 26% has been reduced, with only one early death occurring in the last eight patients; prior cardiac surgery was a contributing factor in three of the six patients suffering early deaths. Two late deaths occurred in the series 14 and 15 months after operation. One patient died suddenly as a result of an acute myocardial infarct and the other patient died because of respiratory failure. At autopsy, both patients had severe proliferative coronary atherosclerosis with obliterative bronchiolitis affecting the lungs. An additional patient required a retransplant for obliterative bronchiolitis 37 months after the initial procedure, and he too was found to have severe coronary artery disease. Hemodynamics and left ventricular function were normal in patients studied 1 and 2 years after undergoing the transplantation procedure. Thus, the early mortality and morbidity of combined heart and lung transplantation has been significantly reduced, but the long-term complications, particularly graft atherosclerosis and obliterative bronchiolitis, are yet to be fully controlled.

    View details for Web of Science ID A1985AGC5100012

    View details for PubMedID 3921277

  • NONINVASIVE ASSESSMENT OF CARDIAC ALLOGRAFT-REJECTION TRANSPLANTATION PROCEEDINGS Dawkins, K. D., Oldershaw, P. J., Billingham, M. E., Hunt, S. A., Jamieson, S. W., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 17 (1): 215-217
  • CYCLOSPORINE IN HEART AND HEART-LUNG TRANSPLANTATION CANADIAN JOURNAL OF SURGERY Modry, D. L., Oyer, P. E., Jamieson, S. W., Stinson, E. B., Baldwin, J. C., Reitz, B. A., Dawkins, K. D., McGregor, C. G., Hunt, S. A., Moran, M., Myers, B., Shumway, N. E. 1985; 28 (3): 274-?


    At Stanford University Medical Center from January 1968 until January 1984, 288 patients received 313 heart transplants. The immunosuppressive regimen before December 1980 consisted of azathioprine and prednisone, with or without rabbit antithymocyte globulin. After that time cyclosporine replaced azathioprine. In 92 recipients of 95 heart allografts, the 1- and 3-year survival rates were 82% and 65% to 70% respectively. In the 3 years from March 1981 to March 1984, successful heart-lung transplantation was accomplished in 13 of 19 recipients, using cyclosporine-based immunosuppression. Survival ranged from 1 to 38 months. While it is true that cyclosporine has improved survival in heart transplant recipients, has allowed successful heart-lung transplantation to be performed, has shortened intensive care unit and total hospital stays and therefore hospital costs, and has allowed easier management of rejection and infection, several disconcerting problems have not yet been resolved. These include hypertension that is difficult to control and renal dysfunction in all patients, and the fact that cellular and humoral rejection still occurs, as manifested by graft atherosclerosis, bronchiolitis obliterans and classic acute rejection. Better understanding and application of cyclosporine immunosuppression will undoubtedly minimize both cyclosporine- and non-cyclosporine-related postoperative complications and will improve survival even further.

    View details for Web of Science ID A1985AHW9000026

    View details for PubMedID 3922606

  • HEART AND LUNG TRANSPLANTATION FOR PULMONARY-HYPERTENSION AMERICAN JOURNAL OF SURGERY Jamieson, S. W., Stinson, E. B., Oyer, P. E., Theodore, J., Hunt, S., Dawkins, K., Billingham, M., Shumway, N. E. 1984; 147 (6): 740-742


    Seventeen patients received combined heart and lung transplants at Stanford University between March 1981 and December 1983. All recipients were suffering from end-stage pulmonary hypertension. Five patients died within the first few postoperative weeks, but the remainder were well between 2 and 35 months after operation. Immunosuppression consisted of cyclosporine with an initial course of rabbit antithymocyte globulin, and azathioprine was given for the first 2 postoperative weeks. Maintenance immunosuppression was achieved with cyclosporine and prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with intravenous methylprednisolone. The functional status of the survivors has been good, and upon discharge from the hospital, all returned to normal activity. Our preliminary experience indicates that cardiopulmonary transplantation represents a realistic therapeutic approach for patients with end-stage pulmonary disease.

    View details for Web of Science ID A1984SX48800007

    View details for PubMedID 6428246

  • CLINICAL HEART-LUNG TRANSPLANTATION TRANSPLANTATION Jamieson, S. W., Baldwin, J., Stinson, E. B., Reitz, B. A., Oyer, P. E., Hunt, S., Billingham, M., Theodore, J., Modry, D., BIEBER, C. P., Shumway, N. E. 1984; 37 (1): 81-84


    Combined heart and lung transplantation was carried out in thirteen patients at Stanford University between March 1981 and May 1983. The recipients were between 22 and 45 years old. All patients were suffering from end-stage pulmonary hypertension; nine patients had Eisenmenger's syndrome; the remaining four were transplanted for primary pulmonary hypertension. Three patients died within one month of surgery. The remainder are well at between 22 months and three weeks from operation. The duration of stay in the hospital for the surviving patients ranged from 38 to 85 days. The immunosuppressive protocol has been essentially the same for all recipients, and has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin (RATG) with azathioprine given for the first two weeks, and then replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with pulses of methylprednisolone. Early complications included bleeding that necessitated reexploration (five patients); damage to the vagus, recurrent laryngeal, or phrenic nerves (three patients); and failure of the donor lungs (one patient). Modifications of technique that have developed include removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution. The results of this operation are considerably superior to clinical efforts in lung transplantation. The combined operation may be preferable for the following reasons: All diseased tissue is removed, thus eliminating recurrent infection, and also perfusion/ventilation disparity. Transplantation of the entire heart and lung block preserves coronary-tracheal vascular anastomoses and makes airway dehiscence less likely. Diagnosis of rejection by cardiac biopsy seems to be a satisfactory method of diagnosis and treatment of pulmonary rejection.

    View details for Web of Science ID A1984RZ82600022

    View details for PubMedID 6420957

  • HEART-LUNG TRANSPLANTATION FOR IRREVERSIBLE PULMONARY-HYPERTENSION ANNALS OF THORACIC SURGERY Jamieson, S. W., Stinson, E. B., Oyer, P. E., Reitz, B. A., Baldwin, J., Modry, D., Dawkins, K., Theodore, J., Hunt, S., Shumway, N. E. 1984; 38 (6): 554-562


    Combined heart and lung transplantation was carried out in 17 patients at Stanford University between March, 1981, and December, 1983. The recipients were between 22 and 45 years old. All patients had end-stage pulmonary hypertension; 10 had Eisenmenger's syndrome and the remaining 7, primary pulmonary hypertension. Five patients died within the first few postoperative weeks. The remainder are well between four weeks and 33 months from operation. The immunosuppressive protocol has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin. Azathioprine also was given for the first two weeks and then was replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with high doses of methylprednisolone. Modifications of technique that have developed include the removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution. Rejection occurred in 6 of the 12 survivors. Infections developed in 9 patients, but only one resulted in a fatal outcome (Legionella). Thus, the results of clinical heart-lung transplantation have been considerably superior to clinical efforts in lung transplantation. It is suggested that the combined operation is preferable for the following reasons: (1) all diseased tissue is removed, thus eliminating recurrent infection and ventilation/perfusion disparity; (2) transplantation of the entire heart-lung block preserves coronary-bronchial vascular anastomoses and makes airway dehiscence less likely; and (3) to date, diagnosis of rejection by cardiac biopsy has appeared to be a satisfactory method of diagnosing and treating pulmonary rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1984TW37500004

    View details for PubMedID 6439134

  • PHYSIOLOGIC ASPECTS OF HUMAN HEART-LUNG TRANSPLANTATION - PULMONARY-FUNCTION STATUS OF THE POST-TRANSPLANTED LUNG CHEST Theodore, J., Jamieson, S. W., Burke, C. M., Reitz, B. A., Stinson, E. B., VANKESSEL, A., Dawkins, K. D., Herran, J. J., Oyer, P. E., Hunt, S. A., Shumway, N. E., Robin, E. D. 1984; 86 (3): 349-357


    Pulmonary function measurements were performed before and after heart-lung transplantation in nine patients who had undergone surgery for end-stage pulmonary hypertension. In seven of them, sequential follow-up studies were performed at variable times postoperatively with the longest period 27 months. Pre-transplant studies showed a mild restrictive defect in 33 percent and obstructive disease in 50 percent of the patients, respectively. Arterial hypoxemia was present in all patients. The degree of mechanical changes found did not appear severe enough to account for the marked dyspnea and disability characterizing this group of patients with pulmonary hypertension. Following transplantation, all patients showed striking improvement of symptoms and general physical status. In the early post-transplant period, there was a marked decrease in most lung volumes resulting in a moderately severe restrictive ventilatory defect. Flow parameters that were reduced could be related to decreased volumes and not to intrinsic airway obstruction. Arterial O2 tensions improved dramatically and gas exchange was maintained at essentially normal levels. Lung function tended to improve progressively following transplantation with the passage of time. Heart-lung transplant is consistent with an adequate long-term pulmonary functional state which has the capacity to sustain the normal activities of daily living. From the standpoint of lung function, heart-lung transplantation appears to be acceptable as a form of therapy in selected patients.

    View details for Web of Science ID A1984TG73000007

    View details for PubMedID 6432455

  • CYCLOSPORIN-A IN CARDIAC ALLOGRAFTING - A PRELIMINARY EXPERIENCE TRANSPLANTATION PROCEEDINGS Oyer, P. E., Stinson, E. B., Jamieson, S. W., Hunt, S. A., Billingham, M., Scott, W., BIEBER, C. P., Reitz, B. A., Shumway, N. E. 1983; 15 (1): 1247-1252
  • CYCLOSPORINE IN CARDIAC TRANSPLANTATION - A 2-1/2 YEAR FOLLOW-UP TRANSPLANTATION PROCEEDINGS Oyer, P. E., Stinson, E. B., Jamieson, S. W., Hunt, S. A., Perlroth, M., Billingham, M., Shumway, N. E. 1983; 15 (4): 2546-2552
  • DIAGNOSIS AND TREATMENT OF ALLOGRAFT-REJECTION IN HEART-LUNG TRANSPLANT RECIPIENTS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Reitz, B. A., Gaudiani, V. A., Hunt, S. A., Wallwork, J., Billingham, M. E., Oyer, P. E., Baumgartner, W. A., Jamieson, S. W., Stinson, E. B., Shumway, N. E. 1983; 85 (3): 354-361


    Six patients received heart-lung transplants between March, 1981, and January, 1982. There were four women and two men between 26 and 45 years of age, three with primary pulmonary hypertension and three with congenital heart disease and pulmonary hypertension (Eisenmenger's syndrome). Immunosuppression was primarily with cyclosporin-A, with additional corticosteroid, azathioprine, and rabbit antihuman thymocyte globulin. Six episodes of allograft rejection in four patients (10, 11, 21, 24, 53, and 86 days after transplantation) were detected by means of transvenous endomyocardial biopsy. All patients experienced pulmonary edema early after transplantation (reimplantation response), and two patients required mechanical ventilatory support for allograft rejection at 10 and 11 days. Treatment of rejection consisted of intravenous methylprednisolone (four episodes) or augmented oral prednisone (two episodes), with resolution. No episode thought to be pulmonary rejection has occurred in the absence of cardiac findings. Four patients are alive from 6 to 15 months after transplantation and are functionally normal. Early experience with heart-lung transplantation suggests (1) that allograft rejection can be detected by cardiac findings and successfully treated by augmented corticosteroids, (2) that lung rejection does not occur in the absence of cardiac findings, (3) that the frequency and severity of rejection episodes are not greater than with standard cardiac transplantation, and (4) that the frequency of rejection episodes is highest within the first 60 days after transplantation.

    View details for Web of Science ID A1983QG01700005

    View details for PubMedID 6402622

  • COMBINED HEART AND LUNG TRANSPLANTATION LANCET Jamieson, S. W., Baldwin, J., Reitz, B. A., Stinson, E. B., Oyer, P. E., Hunt, S., Billingham, M., Theodore, J., Modry, D., BIEBER, C. P., Shumway, N. E. 1983; 1 (8334): 1130-1132


    Combined heart and lung transplantation was carried out in ten patients at Stanford University Medical Center between March, 1981, and December, 1982. All patients had end-stage pulmonary hypertension. 7 of them had Eisenmenger's syndrome and 3 primary pulmonary hypertension. 3 patients died within a month of operation, but the remaining recipients are well 2 months to 2 years after transplantation. The hospital stay of the survivors ranged from 38 to 85 days. All survivors have returned to normal activity. The results of heart and lung transplantation have thus been considerably superior to those reported previously for lung transplantation. It is suggested that cardiopulmonary replacement is suitable treatment for end-stage pulmonary hypertension with or without associated congenital heart disease and that its application to other forms of advanced pulmonary failure may be warranted.

    View details for Web of Science ID A1983QQ80700005

    View details for PubMedID 6133156

  • CLINICAL HEART-LUNG TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Reitz, B. A., Hunt, S. A., GAUDIANI, V., Wallwork, J., Oyer, P. E., Baumgartner, W. A., Jamieson, S. W., Stinson, E. B., Shumway, N. E. 1983; 15 (1): 1256-1259
  • CARDIOVASCULAR PHYSIOLOGY IN A CASE OF HETEROTOPIC CARDIAC TRANSPLANTATION AMERICAN JOURNAL OF CARDIOLOGY MELVIN, K. R., Pollick, C., Hunt, S. A., McDougall, R., Goris, M. L., Oyer, P., Popp, R. L., Stinson, E. B. 1982; 49 (5): 1301-1307


    Successful heterotopic cardiac transplantation in a 24 year old man with end stage cardiomyopathy provided an opportunity to study cardiovascular physiology. The donor and native hearts, functioning independently in parallel, were studied by serial physical examination, electrocardiography, echocardiography, nuclear angiography and cardiac catheterization. Results indicated that the donor left heart assumed the predominant role in supplying systemic output, possibly contributing to decreasing function of the patient's own (native) heart. Analysis of serial nuclear angiograms revealed an initial postoperative ejection fraction of 52 and 21 percent in the donor and the native left ventricle, respectively; repeat studies 3 months postoperatively showed values of 50 and 9 percent, respectively, indicating significant deterioration in native left ventricular cardiac function. Observation of valve motion of the native heart showed major irregularities of the aortic valve in contrast to seemingly normal, regular mitral valve motion. These data rise interesting questions regarding interpretation of valve motion as an indicator of ventricular function.

    View details for Web of Science ID A1982NH12800029

    View details for PubMedID 7039290



    We report our initial experience with three patients who received heart-lung transplants. The primary immunosuppressive agent used was cyclosporin A, although conventional drugs were also administered. In the first patient, a 45-year-old woman with primary pulmonary hypertension, acute rejection of the transplant was diagnosed 10 and 25 days after surgery but was treated successfully; this patient still had normal exercise tolerance 10 months late. The second patient, a 30-year-old man, underwent transplantation for Eisenmenger's syndrome due to atrial and ventricular septal defects. His graft was not rejected, and his condition was markedly improved eight months after surgery. The third patient, a 29-year-old woman with transposition of the great vessels and associated defects, died four days postoperatively of renal, hepatic, and pulmonary complications. We attribute our success to experience with heart-lung transplantation in primates, to the use of cyclosporin A, and to the anatomic and physiologic advantages of combined heart-lung replacement. We hope that such transplants may ultimately provide an improved outlook for selected terminally ill patients with pulmonary vascular disease and certain other intractable cardiopulmonary disorders.

    View details for Web of Science ID A1982ND99400001

    View details for PubMedID 6799824



    Based on the Stanford series of 188 patients, we emphasize that orthotopic cardiac transplantation represents a reasonable therapeutic option for the patient with inoperable end-stage heart disease. Current expectations for survival equal those for organ survival in cadaver renal transplant series and offer a rehabilitation potential of over 90%. Most of the complications limiting survival are due to the currently available means of immunosuppression and, therefore, advances in the field of immunosuppression can be expected to have a major positive influence on survival rates.

    View details for Web of Science ID A1981LH58600016

    View details for PubMedID 7013663

  • COMPLICATIONS IN LONG-TERM SURVIVORS OF CARDIAC TRANSPLANTATION TRANSPLANTATION PROCEEDINGS BIEBER, C. P., Hunt, S. A., Schwinn, D. A., Jamieson, S. A., Reitz, B. A., Oyer, P. E., Shumway, N. E., Stinson, E. B. 1981; 13 (1): 207-211

    View details for Web of Science ID A1981LF81600046

    View details for PubMedID 7022823

  • LONG-TERM SURVIVAL AND FUNCTION AFTER CARDIAC TRANSPLANTATION ANNALS OF SURGERY Gaudiani, V. A., Stinson, E. B., Alderman, E., Hunt, S. A., Schroeder, J. S., Perlroth, M. G., BIEBER, C. P., Oyer, P. E., Reitz, B. A., Jamieson, S. W., CHRISTOPHERSON, L., Shumway, N. E. 1981; 194 (4): 381-385


    Cardiac transplantation now permits prolonged survival for some patients with otherwise fatal heart disease. This report summarizes the hemodynamic and clinical characteristics of 25 patients who have survived five or more years after cardiac replacement. The average age of the patients at the time of operation was 40 +/- 10 (SD) years; 23 were men. The average duration of survival is 6.7 years, and ranges from five to 10.5 years. Annual cardiac catheterization and clinical follow-up were performed to assess systolic cardiac function, coronary anatomy, and quality of extended rehabilitation. We found that among these long-term survivors, the left ventricular ejection fraction remained constant (0.59 +/- 0.08 one year postoperatively, 0.57 +/- 0.09 at most recent study, p = ns). Segmental wall motion measured by fluoroscopic examination of midwall intramyocardial markers also remained normal. Four of 21 (19%) patients with complete longitudinal studies developed significant graft coronary artery disease. Clinical evaluation revealed that the long-term survivors required fewer than one unscheduled admission to the hospital per year. Sixteen of 25 patients (64%) were gainfully employed, and 22 of 25 (88%) enjoyed substantial benefit in terms of extended rehabilitation. These 25 long-term survivors represent 27% of 92 patients transplanted between 1968 and 1975. The actuarial survival rate at five years, of patients transplanted since 1975, is 40 +/- 5%. This increase in survival rate reflects improved techniques of early postoperative management. Cardiac transplantation now offers prolonged survival with good quality of life for selected patients with terminal heart disease.

    View details for Web of Science ID A1981ML08000002

    View details for PubMedID 7025768



    Malignant disease in the mediastinum often presents as superior vena cava syndrome. In this emergency setting, expeditious tissue diagnosis is frequently of extreme importance. We report a case where tissue diagnosis was obtained by cardiac biopsy technique.

    View details for Web of Science ID A1980KH98700009

    View details for PubMedID 6893812

  • SUCCESSFUL RETRANSPLANTATION OF HUMAN HEART JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Copeland, J. G., Griepp, R. B., BIEBER, C. P., Billingham, M., Schroeder, J. S., Hunt, S., Mason, J., Stinson, E. B., Shumway, N. E. 1977; 73 (2): 242-247


    Cardiac retransplantation has been performed in five patients at Stanford University Medical Center. Long-term survival and rehabilitation have been achieved in two cases. In the first case retransplantation was performed 57 days after the initial procedure because of persistent acute graft rejection. The second patient underwent retransplantation 27 months postoperatively because of documented accelerated graft atherosclerosis. The major indications for cardiac retransplantation consist of intractable acute rejection and late postoperative graft atherosclerosis. These complications should prompt consideration of cardiac retransplantation in carefully selected cases.

    View details for Web of Science ID A1977CV61800014

    View details for PubMedID 319302

  • Does cardiac transplantation prolong life and improve its quality? An updated report. Circulation Hunt, S. A., RIDER, A. K., Stinson, E. B., Griepp, R. B., Schroeder, J. S., HARRISON, D. C., Shumway, N. E. 1976; 54 (6): III56-60


    The current status of the human cardiac transplant experience at Stanford University Medical Center is presented in order to reassess its role in the treatment of end-stage cardiac disease. Of 109 patients undergoing transplantation at Stanford between January 1968 and August 1976, 44 were still alive as of August 1, 1976. The overall 1- and 2-year survival rates for the series are 52% and 43%, respectively. Sixty-nine patients have survived more than 3 months, and their overall 1- and 2-year survival rates are 80% and 66%, respectively. Of the 3-month survivors, 62 (90%) returned to functional Class I New York Heart Association cardiac status and most of these returned to their pre-illness activities. Of 40 patients selected for transplantation for whom a donor did not become available, 38 were dead in less than 6 months. Complications related to immunosuppression with steroids are currently the major barrier to longer survival and improved rehabilitation postransplantation. On the basis of these data we conclude that cardiac transplantation not only prolongs survival, but can return carefully selected recipients to an active life.

    View details for PubMedID 45827

  • DOES CARDIAC TRANSPLANTATION PROLONG LIFE AND IMPROVE ITS QUALITY - UPDATED REPORT CIRCULATION Hunt, S. A., RIDER, A. K., Stinson, E. B., Griepp, R. B., Schroeder, J. S., HARRISON, D. C., Shumway, N. E. 1976; 54 (6): 56-60
  • STATUS OF CARDIAC TRANSPLANTATION, 1975 CIRCULATION RIDER, A. K., Copeland, J. G., Hunt, S. A., Mason, J., SPECTER, M. J., WINKLE, R. A., BIEBER, C. P., Billingham, M. E., Dong, E., Griepp, R. B., Schroeder, J. S., Stinson, E. B., HARRISON, D. C., Shumway, N. E. 1975; 52 (4): 531-539


    Since December 1967, 263 human cardiac transplant operations have been performed throughout the world. Eighty-two of these were performed at Stanford University Medical Center, In 1974, 27 such operations were performed, 15 at Stanford Survival rates for the entire Standford series are 48% at one year and 25% at three years; survival rates at one and three years for patients surviving the first three critical months after transplantation are 77% and 42%, respectively. Recipients under the age of 55 years, with New York Heart Association Class IV cardiac disability, are selected for transplant procedures according to criteria dictated by experience over the past seven years. A routine immunsuppressive regimen for organ transplantation, incorporating prednisone, azathioprine, and antithymocyte globulin is employed early postoperatively, and prednisone and azathioprine are used for indefinite maintenance therapy. Acute cardiac graft rejection in nearly all recipients is diagnosed by clinical signs, electrocardiographic changes, and percutaneous transvenous endomyocardial biopsy. Ninety-five percent of acute rejection episodes are reversible with appropriate immunosuppressive treatment, but infectious complications are common and have accounted for 56% of all postoperative deaths. The Stanford experience in cardiac transplantation has demonstrated the potential therapeutic value of this procedure. Maximum survival now extends beyond five years. Satisfactory graft function has been documented in long-term surviving patients, the majority of whom have enjoyed a high degree of social and physical rehabilitation.

    View details for Web of Science ID A1975AR26400002

    View details for PubMedID 1098809

Conference Proceedings

  • Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center Montoya, J. G., Giraldo, L. F., Efron, B., Stinson, E. B., Gamberg, P., Hung, S., Giannetti, N., Miller, J., Remington, J. S. OXFORD UNIV PRESS INC. 2001: 629-640


    A total of 1073 infectious episodes (IEs) that occurred in 620 consecutive heart transplantation patients at Stanford Medical Center between 16 December 1980 and 30 June 1996 were reviewed. Infectious complications were a major cause of morbidity and mortality, second only to rejection as the cause of early deaths and the most common cause of late deaths. Of the IEs, 468 (43.6%) were caused by bacteria, 447 (41.7%) by viruses, 109 (10.2%) by fungi, 43 (4.0%) by Pneumocystis carinii, and 6 (0.6%) by protozoa. The largest number of IEs occurred in the lungs (301 [28.1%]). A significant reduction in the incidence of IEs and a delay in presentation after transplantation were observed; these were most likely related to the introduction of new chemoprophylactic regimens during the study period and prevention of significant disease caused by cytomegalovirus.

    View details for Web of Science ID 000170271200007

    View details for PubMedID 11486285

  • Severe tricuspid regurgitation after heart transplantation Chan, M. C., Giannetti, N., Kato, T., Kornbluth, M., Oyer, P., Valantine, H. A., Robbins, R. C., Hunt, S. A. ELSEVIER SCIENCE INC. 2001: 709-717


    Tricuspid regurgitation (TR) is common after heart transplantation. However, the incidence of severe TR and the incidence of symptoms after echocardiographic diagnosis of severe TR have not been documented. The purpose of this study is to determine the incidence of severe TR and its clinical significance in the heart transplant population.We reviewed echocardiograms (echo) of all heart transplant patients coming for regular echocardiographic follow-up between 1990 and 1995. We reviewed the charts of all patients who had echo diagnosis of severe TR.A total of 336 patients had echo follow-up during this time period. The number of months post-heart transplant to last echo was 54 +/- 50 (range, 1 to 265 months). Ninety patients had moderate TR and 23 patients had severe TR. Mean time from heart transplantation to diagnosis of severe TR was 43 +/- 38 months (range, 1 to 132). Using Cutler-Ederer analysis, at 5 years, 92.2% of surviving patients were free from severe TR. At 10 years, 85.8% of surviving patients were free from severe TR. Of the 23 patients with severe TR, 17 had charts available for review. The mean number of prior endomyocardial biopsies was 28 +/- 21 (range, 3 to 88). These patients were followed for 35 +/- 18 months after diagnosis. During this period, they developed significant heart failure and peripheral edema. Six patients eventually underwent tricuspid valve replacement.Moderate to severe TR commonly occurs following heart transplantation. Severe TR is associated with significant morbidity.

    View details for Web of Science ID 000169835400002

    View details for PubMedID 11448795

  • Thirty years of cardiac transplantation at Stanford University Robbins, R. C., Barlow, C. W., Oyer, P. E., Hunt, S. A., Miller, J. L., Reitz, B. A., Stinson, E. B., Shumway, N. E. MOSBY-ELSEVIER. 1999: 939-949


    The experience with 30 years of cardiac transplantation at Stanford University Medical Center was reviewed. A total of 954 transplants were performed in 885 patients. Patients were divided into 3 groups based on immunosuppression received: group I, no cyclosporine (INN: ciclosporin) (n = 201) (January 1968-November 1980); group II, cyclosporine (n = 248) (December 1980-June 1987); and group III, cyclosporine + OKT3 (n = 436) (July 1987-March 1998).The 1-, 5-, and 10-year actuarial survivals were 68%, 41%, and 24% (group I); 80%, 57%, and 37% (group II); and 85%, 68%, and 46% (group III) (I vs II, P <.01; I vs III, P <.005; and II vs III, P <.005). The 1-, 5-, and 10-year actuarial death rates from rejection were 8%, 12%, and 14% (group I); 5%, 7%, and 7% (group II); and 2%, 5%, and 5% (group III) (I vs II, P = not significant; I vs III, P <.005; and II vs III, P <.005). The 1-, 5-, and 10-year actuarial death rates from infection were 25%, 43%, and 50% (group I); 8%, 17%, and 29% (group II); and 6%, 11%, and 16% (group III) (I vs II, P <.005; I vs III, P <.005; and II vs III, P <.05). The 1-, 5-, and 10-year actuarial death rates from graft coronary artery disease were 0%, 5%, and 13% (group I); 0%, 12%, and 19% (group II); and 1%, 6%, and 9% (group III) (I vs II, P <.01; I vs III, P <.005; and II vs III, P = not significant). There have been 69 retransplants in 67 patients with 1-, 5-, and 10-year actuarial survivals of 49%, 27%, and 15%, respectively.The evolution of 3 decades of experience with cardiac transplantation has resulted in improved overall survival. The incidence of rejection and of death from infection and graft coronary artery disease have decreased over time, primarily as a result of improvements in immunosuppression and in the prevention and treatment of infection. Continued advances in perioperative management and the development of more specific, less toxic immunosuppressive agents could further refine this initial experience and improve the survival and quality of life of patients after cardiac transplantation.

    View details for Web of Science ID 000080116000015

    View details for PubMedID 10220689

  • Long-term results of total lymphoid irradiation in the treatment of cardiac allograft rejection Wolden, S. L., Tate, D. J., Hunt, S. A., Strober, S., Hoppe, R. T. ELSEVIER SCIENCE INC. 1997: 953-960


    To evaluate the short and long-term effects of total lymphoid irradiation (TLI) in the treatment of cardiac transplant rejection.Between 1986 and 1995, 48 courses of TLI were delivered to 47 cardiac transplant patients. In 37 patients, TLI was administered for intractable allograft rejection despite conventional therapy while 10 patients received TLI prophylactically. The prescribed radiation dose was 8 Gy in 0.8 Gy fractions twice weekly to mantle and inverted-Y plus spleen fields. Postirradiation follow-up ranged from 6 months to 9.1 years, with a mean of 3.1 years.The actual mean dose was 7.3 Gy delivered over a mean of 39 days. Fifty-six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, rejection rates dropped from 0.46 to 0.14 and to 0.06 episodes/patient/month before, during, and after TLI (p < 0.0001). Rejection rates continued to drop throughout follow-up. Prednisone requirements decreased from 0.41 mg/kg before treatment to 0.21 mg/kg afterward (p < 0.0001). The ratio of helper to cytotoxic-suppressor T-cells decreased during TLI from 1.33 to 0.89, and remained low at 0.44, 2-4 months after treatment. Infection rates were not increased and two patients developed malignancy. Rejection rates were high during prophylactic treatment and this protocol was abandoned. Three-year actuarial survival after irradiation was 60% for patients with intractable rejection and 70% for the prophylactic cohort.TLI is an effective treatment for control of intractable cardiac rejection. Episodes of rejection and steroid dosage requirements are decreased for up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. Long-term complications of TLI are not appreciably different than conventional immunosuppression.

    View details for Web of Science ID A1997YG83800002

    View details for PubMedID 9392531

  • Pulmonary hypertension in severe congestive heart failure: How important is it? Hunt, S. A. MOSBY-YEAR BOOK INC. 1997: S13-S15

    View details for Web of Science ID A1997XK17200020

    View details for PubMedID 9229305

  • Heart transplantation in patients over 54 years of age - Mortality, morbidity and quality of life Rickenbacher, P. R., Lewis, N. P., Valantine, H. A., Luikart, H., Stinson, E. B., Hunt, S. A. W B SAUNDERS CO LTD. 1997: 870-878


    As a consequence of recent advances in heart transplantation, upper age limits for the procedure have been liberalized in many centres. It was the purpose of this study to compare post-transplant mortality, morbidity and quality of life in a consecutive series of 72 patients > 54 years (mean age, 57.6 +/- 2.7 years) with a control group of 72 adult patients < or = 54 years (mean age, 42.4 +/- 9.5 years) transplanted at one centre between 1985 and 1991.Patients were followed for 41 +/- 27 months post-transplant. Actuarial 1-, 5- and 7-year survival rates were 78 +/- 5%, vs 81 +/- 5%, 52 +/- 7% vs 66 +/- 6% and 46 +/- 8% vs 63 +/- 6% in patients > 54 years and < or = 54 years, respectively (P = ns). Causes of death were not significantly different between the groups. Patients > 54 years experienced significantly fewer rejection episodes after the 6th month post-transplant (0.5 +/- 0.9 vs 0.9 +/- 1.0, P < 0.04), and incidence and treatment of rejection episodes as well as incidence of infection was comparable between the groups. Non-lymphoid malignancies, mainly skin cancer, occurred more often in the older age group (27% vs 13%, P < 0.05). Quality of life, as assessed by the Nottingham Health Profile, was better in 5/6 dimensions of social functioning in older patients and the difference reached statistical significance for the dimensions of emotional reactions (P = 0.005) and sleep (P = 0.0005).In conclusion, carefully selected patients > 54 years can undergo heart transplantation with mortality and morbidity comparable to younger patients. Quality of life post-transplant seems even to be slightly better in the older age group.

    View details for Web of Science ID A1997WX06100025

    View details for PubMedID 9152659

  • Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis Reichenspurner, H., Gamberg, P., Nitschke, M., Valantine, H., Hunt, S., Oyer, P. E., Reitz, B. A. ELSEVIER SCIENCE INC. 1997: 627-628

    View details for Web of Science ID A1997WM12700260

    View details for PubMedID 9123449

  • Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus infections after heart transplantation Wagner, J. A., Ross, H., Hunt, S., Gamberg, P., Valantine, H., Merigan, T. C., Stinson, E. B. WILLIAMS & WILKINS. 1995: 1473-1477


    Cytomegalovirus (CMV) infection is associated with an increased incidence of other opportunistic infections in organ transplant recipients. Whether this is related to immunomodulating effects of CMV or independent of CMV but associated with a host risk factor common to both infections is unclear. The purpose of this study was to determine whether the reduction in CMV infections seen with prophylactic ganciclovir treatment after heart transplantation is associated with a reduced incidence of other opportunistic infections. Of 149 patients prospectively enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of ganciclovir to prevent CMV disease, 74 patients enrolled at this center (33 control and 41 ganciclovir-treated) were retrospectively identified. All received prophylactic OKT-3 and standard 3 drug maintenance immunosuppressive therapy. Actuarial survival and rejection rates and incidence of opportunistic infections (bacterial, fungal, and protozoal) for the 2 treatment groups were determined and compared using Cox-Mantel analysis. CMV disease occurred 2.5 times more frequently in the control group. There were no significant differences in survival or rejection rates nor in bacterial or protozoal infection incidence between the 2 groups. Bacterial infections occurred in 54% of control and 39% of ganciclovir-treated patients (P = 0.18). There were significantly fewer fungal infections in the ganciclovir-treated group (7% vs. 27%, P = 0.0071). CMV and fungal infections were both significantly reduced in patients who received ganciclovir prophylaxis. This suggests that active CMV disease may be causally associated with the development of opportunistic fungal infections.

    View details for Web of Science ID A1995TN23000018

    View details for PubMedID 8545877



    The clinical status and quality of life of 40 patients who lived or are still alive more than 10 years after transplantation at our institution were reviewed with the use of our transplant database, prospective patient examinations, cardiac catheterization, and exercise testing. Patient-perceived health status was determined with use of the Nottingham Health Profile and General Well Being examinations. Factors associated with longevity were determined by a Cox proportional hazards model. Twenty-six patients are alive and 14 have died. The mean age at transplant was 32.4 +/- 12 years and the current age (or age at death) is 46.1 +/- 12.8 years. Actuarial freedom from rejection was similar to that of patients surviving less than 10 years (p = 0.8), but freedom from all types of infection was less (p = 0.005). Immunosuppressive drugs include cyclosporine (11/26 patients), azathioprine (24/26), and prednisone (26/26, mean dose 12.7 mg/day). Catheterization hemodynamic data show well-preserved graft function at a mean follow-up of 11.7 +/- 3.3 years. Graft coronary artery disease prevalence is 51.0% +/- 8%. Exercise test results are as follows: duration 8.7 +/- 3.5 minutes (range 2 to 16 minutes), maximum heart rate/expected rate 77.3% +/- 11% (50% to 92%), maximum systolic blood pressure 171 +/- 23 mm Hg (140 to 208 mm Hg), and metabolic equivalents 9.2 +/- 2.3 units (5.5 to 12.9 units), or about 84% of predicted. Mean score on the General Well Being examination was 75.3 +/- 21.6 (normal). Nottingham Health Profile scores were nearly normal, except for in the 50- to 64-year-old age group in categories of mobility, pain, sleep quality, and energy level. Causes of death were coronary artery disease in 7 of 14, infection in 4 of 14, lymphoma in 1 of 14, and nonlymphoid cancer in 2 of 14. In the Cox regression, variables most associated with survival (t > 2.0, multivariate p = 0.0005) were age at transplantation (t = 3.26), preoperative duration of illness (t = 3.57), postoperative cytomegalovirus infection (t = 2.16), and ejection fraction at 12 months after operation (t = -2.62). We conclude that cardiac transplantation can provide patients with end-stage cardiac failure an acceptable general medical condition, functional status, and perceived quality of life well into the second decade after operation.

    View details for Web of Science ID A1995RC74000010

    View details for PubMedID 7776675


    View details for Web of Science ID A1994PM60300142

    View details for PubMedID 7940898


    View details for Web of Science ID A1994PM60300089

    View details for PubMedID 7940848



    To assess survival after the development of transplant coronary artery disease, annual angiography reports from 353 heart transplant recipients were reviewed. Fifty-four patients who survived beyond 1 year and in whom moderate-to-severe proximal or midvessel coronary artery disease developed were identified. Moderate-to-severe proximal or midvessel coronary disease was defined for this study as a 40% or more stenosis in 1 or more primary or secondary epicardial arteries. Actuarial survival (Kaplan-Meier) from the time of disease detection in those 54 patients was 67% at 1 year, 44% at 2 years, and 17% at 5 years. Actuarial survival was reduced proportionate to disease severity. Survival for single-vessel disease (> or = 40% stenosis) was 64% at 1 year, 36% at 2 years, and 22% at 5 years. Survival was significantly worse with triple-vessel disease (13% at 2 years; p = 0.01) and intermediate for double-vessel disease (41% at 2 years; p = 0.01). Of 19 patients who underwent retransplantation for coronary artery disease, 13 patients (68%) died at a mean of 24 +/- 20 months (range, 1 to 59), and of 15 patients from whom postmortem or angiographic data were available, 11 patients (73%) showed recurrence of significant coronary artery disease in the new graft. Identification of moderate or severe proximal or midvessel coronary disease at angiography predicts an overall mortality rate of more than 50% at 2 years. The poor survival rate in those who underwent retransplantation (around 50% at 4 years) and the high rate of redevelopment of coronary disease suggest that retransplantation should be reserved for selected candidates with angiographically severe disease, if used at all.

    View details for Web of Science ID A1992JR77000007

    View details for PubMedID 1420237



    Accelerated graft coronary artery disease (CAD) has become a major factor limiting survival among long-term heart transplant survivors. Currently 14%, 37%, and 50% of patients treated with triple therapy have angiographically apparent accelerated graft CAD at 1, 3, and 5 years after transplantation. Because cardiac allografts are denervated, transplant recipients generally do not experience angina pectoris. Therefore accelerated graft CAD may present as silent myocardial infarction, congestive heart failure, or ventricular arrhythmia leading to syncope or sudden death. Noninvasive tests for CAD have been insensitive for the detection of accelerated graft CAD because of the diffuse nature of the disease. Coronary arteriographic characteristics of accelerated graft CAD are a mixture of typical focal atherosclerotic lesions and unusual diffuse, concentric, and longitudinal narrowing prominent in middle to distal coronary vessels, with distal vessel obliteration and lack of collateral vessel formation. The presence and severity of accelerated graft CAD may be underestimated by routine angiography because of its diffuse and concentric nature. Quantitative arteriography has become an important technique to assess the progression of accelerated graft CAD. Intravascular ultrasound imaging can detect even earlier development of intimal thickening. CAD risk factor modification has had little impact on the overall incidence. We initiated a randomized study of diltiazem versus no calcium blocker to determine if this may prevent accelerated graft CAD. Patients have undergone early postoperative and annual quantitative coronary angiography since inception of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1992JJ43700019

    View details for PubMedID 1515448



    A retrospective review was undertaken to determine the clinical features, outcome, and impact on survival of nontuberculous mycobacterial infections in 14 (of 502) heart transplant recipients. The prevalence of these infections was significantly higher (p less than 0.05) during the precyclosporine than during the cyclosporine era. The mean interval from transplantation to diagnosis was 3.5 +/- 0.7 years (+/- SEM). The 14 patients had a higher (p less than 0.05) linearized rejection rate than did other transplant patients during postoperative years 1, 2, and 4 to 6, and had received 7.3 +/- 2 gm of methylprednisolone as bolus treatment of rejection before diagnosis. Eight patients were initially seen with disseminated disease, four had localized pulmonary infection, one had subcutaneous infection in the previous site of a left ventricular assist device, and in one the organism was cultured from a fluid collection adjacent to a hip prosthesis. Twelve patients were first given 3 +/- 1 antimycobacterial drugs; the infections were usually controlled, but in 75% of patients the therapeutic regimen was prematurely stopped or altered because of drug toxicity. Mycobacterial infection was a contributory cause of death in only one patient. Actuarial survival in the 14 patients was not significantly different from the entire transplant population at 4 to 7 years. We conclude that nontuberculous mycobacterial infections occur late after heart transplantation, that drug treatment is usually successful (although difficult), and that long-term survival is not adversely affected if the infection is successfully controlled.

    View details for Web of Science ID A1990DT02600006

    View details for PubMedID 2398429


    View details for Web of Science ID A1990DM53300002

    View details for PubMedID 2349732

Stanford Medicine Resources: