Selecting oversized donor cardiac allografts for patients with pulmonary hypertension may be unnecessary.

INTRODUCTION: There is a tendency to favor oversized donor hearts for heart transplant candidates affected by mild to moderate pulmonary hypertension (PHTN). We hypothesize that both undersized and oversized donor hearts fare equally well in this setting. METHODS: A total of 107 cases from 2003 to 2008 were retrospectively reviewed and subsequently divided into those receiving organs from undersized donors (group 1: donor weight/recipient weight ≤ 0.90, n = 37) and oversized donors (group 2: donor weight/recipient weight ≥ 1.2, n = 70). PHTN was identified in the perioperative period in those patients with systolic pulmonary artery pressure (SPAP) ≥ 40 mm Hg. Endpoints of mortality and hemodynamic data were investigated. RESULTS: Of 107 patients, 37 received undersized donor allografts, with a mean donor-to-recipient weight ratio of 0.8, and 70 received oversized donors allografts, with a mean donor-to-recipient ratio of 1.4. Perioperative PAH was diagnosed in 20 of the 37 (54%) patients from the undersized group (mean SPAP = 45.9 mm Hg) and 41 of 70 (59%) patients from the oversized group (mean SPAP = 46.5 mm Hg). There was no significant difference in right ventricular function at 1 week, 1 month, or 6 months. Left ventricular function was similar between both groups at 6 months (P = .22). The mean SPAP in the undersized group was 45.9, 33.4, 31.8, and 23.1 mm Hg at the perioperative, 1 week, 1 month, and 6 month time points, respectively. Corresponding mean SPAP for the oversized group was 46.5, 35.0, 29.4, and 26.1 mm Hg. The 1 month, 1 year, and 3 year survivals were similar in both groups. CONCLUSIONS: Oversized and undersized donor hearts fared equally well in the setting of mild to moderate perioperative PAH. This in addition to the propensity for resolution of pulmonary hypertension over time suggests that the current practice of favoring oversized donor hearts for patients with pre-transplantation PAH may be unwarranted.

Donor brain death mechanisms and outcomes after heart transplantation.

We sought to explore whether the cause of donor brain death influenced recipient outcomes after cardiac transplantation. In retrospect, 358 consecutive donors provided cardiac allografts to adult patients undergoing orthotopic heart transplantation at a single urban US medical center from January 2000 through December 2005. Alternate recipients were excluded. Mechanism and cause of donor brain injury and death were divided into five categories: anoxia (nontraumatic) (n=36), blunt head trauma (n=220), penetrating head trauma (n=83), brain tumor/infection (n=7), and cerebrovascular event (n=12). The five subgroups were categorized as traumatic or nontraumatic. The end points of the study were causes of early and late mortality, survival, and rejection rate. There were 59 deaths in the 6-year period. Total and short-term recipient mortality were found to be statistically higher among heart transplant recipients when the donors suffered from traumatic brain death compared to those whose brain death etiology was nontraumatic (P=.045, P=.033, respectively). Rejection rate was similar in all groups (P=.497). In conclusion, donor traumatic brain death was found to be a valid risk factor for recipient mortality after heart transplantation. Caution should be used when evaluating such donors, particularly in the presence of other risk factors.

Ethnicity as a predictor of graft longevity and recipient mortality in heart transplantation.

BACKGROUND: There is a dearth of data about the effect of donor and recipient ethnicity on survival and rejection rate after clinical heart transplantation, although the subject had been partly studied before. We compared the mortality and rejection rate among different ethnic groups at our institution. METHODS: In retrospect, 525 consecutive donors provided cardiac allografts to adult and pediatric patients undergoing orthotropic heart transplantation at a single, urban US medical center between 2000 and 2005. Donors and recipients were categorized according to ethnicity: African American, Asian, Caucasian, Hispanic, and Others (Indian, Mediterranean/Arabic, Afghans). Donor and recipient ethnicity-as an independent factor and the interaction between them-were examined as a risk factor for mortality and rejection after heart transplantation. Mean follow-up period was 3.2+/-1.9 years (range, 0.1 to 6.6). All recipients received triple immunosuppression consisting of a calcineurin inhibitor, an antiproliferative agent, and steroids. No patients received induction immunotherapy. The end points of the study were early and late mortality, rejection rate, and rejection-free survival time. RESULTS: The overall mortality was 17.3% (91 patients). Recipient mortality rate according to donor race was: African American, 23.1%; Asian, 11.1%; Caucasian, 18.7%; and Hispanic, 14.6%. No statistical significance was found, although the mortality differences presented. Recipient mortality with regard to recipients ethnicity was: African American, 22.2%; Asian, 6.3%; Caucasian, 18%; Hispanic, 18.9%; and others 40% (P=.048). Donor-recipient race match was not found as a risk factor influencing mortality as the matched group mortality was 17.5% comparing with the mismatched group mortality of 17.8% (P=.874). The overall rejection rate was 3.8% (20 rejection events). Rejection rate according donor race was: African American, 7.7%; Asian, 10.7%; Caucasian, 4%; and Hispanic, 1.3% (P=.027). Rejection rate with respect to recipients ethnicity was: African American, 0; Asian, 3.2%; Caucasian, 4.4%; Hispanic, 2.7%; and others, 20% with no statistical significance (P=.236). Donor recipient race match was not found as a risk factor influencing rejection rate (P=.58). CONCLUSIONS: Recipients' ethnicity was found as a significant risk factor for mortality. Rejection rate were found higher among the African American donors and significantly lower in the Hispanic donors. Significantly lower mortality rate was found among Asian recipients. Donor-recipient race match did not influence the mortality or rejection rate.

Is third-time heart retransplantation justifiable?

Since repeat heart transplantation traditionally carries higher risk than primary engraftment, we tested the hypothesis that third-time cardiac allograft transplantation is associated with prohibitive mortality and morbidity. The cohort of all third-time cardiac retransplants performed at our institution (n=3) and reported to UNOS from 1987 to 2002 (n=10) was reviewed. The primary endpoints were early and late mortality. Extending the study frame through 2003 captures a total of 5 and 15 third-time heart transplant recipients in UCLA and UNOS databases, respectively. Of the 15 patients undergoing third-time retransplants, preoperatively one was ventricular assist device-dependent, four were on intravenous inotropes, and two had creatinine levels greater than 2.5. Additionally, four were male recipients of female donor hearts and the mean donor ischemic time was 2.6 hours. One patient was diagnosed with acute allograft rejection, 13 with coronary artery vasculopathy/chronic rejection, and one with primary graft failure. At our institution, five patients underwent a third heart transplant. There was no early or hospital mortality. One patient died late from transplant coronary artery disease and another following a fourth allograft. The mortality rate for third-time heart allograft recipients is acceptable. These results are influenced by small sample size, younger age, case selection, and operations at select, high-volume institutions with significant experience.

Five-year results of a randomized, single-center study of tacrolimus vs microemulsion cyclosporine in heart transplant patients.

BACKGROUND: Previous multicenter, randomized trials, lacking standardized post-transplant protocols, have compared tacrolimus (Tac) and cyclosporine (CyA, Sandimmune) and demonstrated similar outcomes with some different adverse effects. The microemulsion form of CyA (mCyA, Neoral) has replaced Sandimmune CyA as the more widely utilized CyA formulation. This is the first 5-year follow-up study of a large, single-center trial (n = 67) under a standardized post-transplant protocol comparing Tac and mCyA. METHODS: Sixty-seven heart transplant patients were randomized to Tac (n = 33) or mCyA (n = 34), both in combination with corticosteroids and azathioprine without cytolytic induction. Five-year end-points included survival, Grade > or = 3A or treated rejection, angiographic cardiac allograft vasculopathy (CAV; any lesion > or = 30% stenosis), renal dysfunction (creatinine > or = 2.0 mg/dl), use of two or more anti-hypertensive medications, percent diabetic and lipid levels. RESULTS: Five-year survival, freedom from Grade > or = 3A or any treated rejection and angiographic CAV, mean cholesterol level and percent diabetic were similar between the two groups. The Tac group had a significantly lower 5-year mean triglyceride level (Tac 97 +/- 34 vs mCyA 175 +/- 103 mg/dl, p = 0.011) and average serum creatinine level (Tac 1.2 +/- 0.5 mg/dl vs mCyA 1.5 +/- 0.4 mg/dl, p = 0.044). There was a trend toward fewer patients requiring two or more anti-hypertensive drugs in the Tac group (Tac 33% vs mCyA 59%, p = 0.065). CONCLUSIONS: Tac and mCyA appear to be comparable with regard to 5-year survival, freedom from rejection and CAV. However, compared with mCyA, Tac appears to reduce the adverse effect profile for hypertriglyceridemia and renal dysfunction and the need for hypertensive medications.

Right ventricular outflow tract transannular patch placement without cardiopulmonary bypass.

In children with pulmonary atresia not amenable to initial complete correction, antegrade pulmonary blood flow can be established with surgical right ventricular outflow tract (RVOT) patch enlargement. An 11-year experience with RVOT transannular patch (TAP) augmentation without the use of cardiopulmonary bypass (off-pump) is reported. From March 1993 to October 2004, off-pump surgical RVOT enlargement with a TAP was attempted in all patients in whom a concurrent procedure that required bypass was not required. The procedure was performed with cardiopulmonary bypass standby. Twenty-two consecutive patients in whom this procedure was attempted were reviewed. Twenty of 22 patients tolerated off-pump TAP placement. In 2 patients with ductal-dependent pulmonary blood flow, off-pump TAP placement was not tolerated. Adequate antegrade pulmonary blood flow was achieved in all patients without operative mortalities or complications. There was one death in the postoperative period from myocardial ischemia secondary to right ventricular-dependent coronary circulation. Transannular RVOT patch augmentation can be performed safely and effectively without cardiopulmonary bypass.

Local delivery of mithramycin restores vascular reactivity and inhibits neointimal formation in injured arteries and vascular grafts.

Arterial restenosis is responsible for the high failure rates of vascular reconstruction procedures. Local sustained drug delivery has shown promise in the prevention of restenosis. The drug release rate from mithramycin-loaded EVA matrices (0.1%) was evaluated, and their antirestenotic effect was studied in the rat carotid model and rabbit model of vascular grafts. The modulation of c-myc expression by mithramycin treatment was examined by immunohistochemistry in the rat carotid model. The proliferative response of injured rat arteries was studied by bromdeoxyuridine (BrdU) immunostaining. The impact of mithramycin treatment on vasomotor responses of the venous segments grafted into arterial circulation was studied ex vivo using vasoreactive compounds. Mithramycin was released exponentially from EVA matrices in PBS. Matrices co-formulated with PEG-4600 revealed enhanced release kinetics. The perivascular implantation of drug-loaded EVA-PEG matrices led to 50% reduction of neointimal formation, and reduced the c-myc expression and BrdU labeling in comparison to control implants. Decreased sensitivity of mithramycin-treated grafts to serotonin-induced vasoconstriction was observed. Local perivascular mithramycin treatment limits the functional alteration caused by the grafting of venous segments in high-pressure arterial environment, and potently inhibits stenosis secondary to grafting and angioplasty injury. The antirestenotic effect is associated with reduced c-myc expression and with subsequent decrease in SMC proliferation.

Inhaled nitric oxide for pulmonary hypertension after heart transplantation.

BACKGROUND: Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide (NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group. METHODS: Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension. RESULTS: Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05). CONCLUSION: In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.

Efficiency, efficacy, and adverse effects of adenovirus vs. liposome-mediated gene therapy in cardiac allografts.

Virus- and nonvirus-mediated immunosuppressive cytokine gene therapy prolongs cardiac allograft survival in various nonfunctional heart transplant animal models, but its cardiac adverse effects have not been addressed. Recently, we developed a functional heterotopic heart transplant model in rabbits. For the first time, we were able to systematically compare the efficiency, efficacy, and adverse effects of optimized adenovirus- and liposome-mediated ex vivo interleukin (IL)-10 gene transfer in functional donor hearts. The efficiency of liposome-mediated gene transfer was greatly improved in physiologically functioning donor hearts and was only three- to fourfold lower than adenovirus-mediated gene transfer. The efficacy of liposome-mediated IL-10 gene transfer was much higher than that mediated by adenovirus. Significant negative inotropic and arrhythmogenic adverse effects on transplanted hearts were observed due to viral cytotoxicity and immunogenesis, which greatly abated the therapeutic efficacy of this first generation adenovirus-mediated gene therapy.

Rantes production during development of cardiac allograft vasculopathy.

BACKGROUND: RANTES (regulated on activation, normal T cell expressed and secreted) production has been shown to correlate with mononuclear cell recruitment and precede intimal thickening in cardiac allograft vasculopathy (CAV). However, the cells that produce RANTES in CAV are undefined. Therefore, in an MHC II-mismatched murine model of CAV, we sought to (1) define the cellular sources of RANTES and (2) determine the role of CD4+ lymphocytes in RANTES production during CAV development. METHODS: B6.CH-2bm12 strain donor hearts were transplanted heterotopically into wild-type (WT) or CD4 knockout (CD4KO) C57BL/6 mice (MHC II mismatch). No immunosuppression was used. Recipients were sacrificed at 7, 14, and 24 days. Intragraft RANTES gene expression and protein levels were determined with ribonuclease protection assay and ELISA, respectively. At days 7 and 24, RANTES production by graft-infiltrating cells was defined with intracellular RANTES staining and multicolor FACS analysis. Intimal thickening was quantitated morphometrically. In murine hearts and in six explanted human hearts with advanced CAV, RANTES was also localized immunohistochemically. RESULTS: NK, NKT, and gammadelta+ cells, in addition to CD4+, CD8+ lymphocytes, and CD11b+ macrophages, produced RANTES in early and late stages of CAV. RANTES-producing NK, NKT, and gammadelta+ cells tripled in number during CAV development; by day 24, NK and gammadelta+ cells each outnumbered CD4+ lymphocytes and CD11b+ macrophages. The presence of CD4+ lymphocytes was required for sustained RANTES production in allografts, which correlated with mononuclear cell recruitment and preceded intimal thickening. In murine and explanted human hearts with advanced CAV, RANTES immunolocalized with graft-infiltrating mononuclear cells and vessel wall cells. CONCLUSIONS: We present evidence that other cell types in addition to CD4+, CD8+ T lymphocytes, and CD11b+ macrophages contribute significantly to RANTES production in CAV. In this MHC II-mismatched murine model of CAV, sustained RANTES production requires CD4+ lymphocytes, correlates with mononuclear cell recruitment, and precedes intimal thickening. In experimental and human CAV, vessel wall cells may also produce RANTES. Interventions aimed at inhibiting RANTES production in CAV may need to target several types of cells, and neutralization of RANTES bioactivity may reduce mononuclear cell recruitment and CAV development.

A prospective trial of inhaled nitric oxide in clinical lung transplantation.

BACKGROUND: Reperfusion injury (RI) is a major cause of mortality and morbidity among lung transplant recipients. We sought to determine if prophylactic administration of inhaled nitric oxide (NO) to lung transplant recipients at reperfusion would prevent RI. We also hypothesized that if prophylactic NO proves ineffective in preventing RI then it may improve pulmonary hemodynamics and gas exchange in the subset of patients who develop RI. METHODS: After informed consent, 28 consecutive, adult lung transplant recipients received NO at 20 ppm at reperfusion. NO was withdrawn for 15 min at 6 and 12 hr after reperfusion, and gas exchange and hemodynamics were measured. RESULTS: Five of the 28 lung transplant recipients (18%) developed RI. Withdrawal of NO for 15 min in this subset of patients resulted in a significant rise in mean pulmonary artery pressure and a reduction in oxygenation index. All five patients with RI were kept on inhaled NO until full functional recovery of the allograft and were then weaned from mechanical ventilation. None required extracorporeal membrane oxygenation support; the early mortality in this group was 20% (1/5). The remaining 23 patients without RI had uneventful early postoperative course and were weaned from NO and mechanical ventilation within 36 hr of transplantation. CONCLUSIONS: Prophylactic-inhaled NO does not prevent RI in human lung transplantation. However, inhaled NO, started at reperfusion, improves gas exchange and reduces pulmonary artery pressure in those patients who develop RI.

Increased incidence of atrial flutter associated with the rejection of heart transplantation.

Atrial fibrillation (AF) and atrial flutter (Afl) are common dysrhythmias that occur after orthotopic heart transplantation (OHT); however, their etiology and clinical significance have not been defined. To determine the precise incidence of sustained AF and Afl and their association with cardiac rejection, 892 consecutive patients who underwent OHT were studied. A total of 104 patients had 113 episodes of Afl; 102 patients had 117 episodes of AF. The incidence of Afl (12.7%) was the same as AF (13.1%). Sixty-nine AF episodes occurred in first 2 weeks after transplantation, and 22 of which were associated with rejection. In contrast, only 20 Afl episodes occurred the first 2 weeks after OHT, 10 of which were associated with rejection. Fifty-two episodes of Afl occurred during from the third week to 6 months after transplantation, 34 of which were associated with moderate to severe cellular or humoral rejection and/or transplant coronary artery disease (TCAD). All 41 Afl episodes that occurred 6 months after transplantation were associated with cellular and humoral rejection, and/or TCAD. The prevalence of Afl was significantly higher in biatrial than bicaval anastomosis. Atrial conduction defect, manifested by the increase of terminal force of the P wave in lead V(1) of the surface electrocardiogram, predicted the occurrence of Afl and AF associated with rejection in OHT with a sensitivity of 89% and specificity of 92%. These results demonstrate that the incidence of Afl increased after OHT, which might be a consequence of cellular and humoral rejection, and coronary vasculopathy of the transplanted hearts.

Heart transplantation in the young and elderly.

INTRODUCTION: Heart transplantation has become an acceptable treatment in pediatric patients with end-stage heart disease and complex congenital heart disease. The liberalization of recipient eligibility criteria, mainly age, along with the expansion of the donor pool has resulted in the acceptable transplantation of older recipients. METHODS: Between July 1994 and June 1998, 39 pediatric patients aged 16 days to 17.6 years (median 6.68 years) and 123 elderly patients aged 60 to 74.8 years (median 64.1 years) were transplanted at our institution. In the pediatric group, 19 had idiopathic dilated cardiomyopathy (DCM) (46 %), 14 had congenital heart disease (34 %), 4 had other etiologies of cardiomyopathy (10 %), 2 had transplant coronary artery disease (TCAD) (5 %), and 1 each had acute rejection and graft failure. In the elderly group, 71 had ischemic cardiomyopathy (58 %), 38 had DCM (31 %), 9 had other forms of cardiomyopathy (7 %), and 5 had TCAD (4 %). RESULTS: Thirty-day, 1-year, and 4-year survival was 97.4 %, 87.2 %, and 70.9 % for the pediatric group and 92.7 %, 81.3 %, and 79.3 % for the elderly group. One and 4-year freedom from TCAD was 100.0 % and 85.3 % for the pediatric group and 91.9 % and 83.3 % for the elderly group. CONCLUSIONS: [emsp3 ]Orthotopic heart transplantation is effective for the treatment of irreparable congenital and end-stage heart disease. It provides excellent long-term results in both the very young and elderly.

CD8+ lymphocytes augment chronic rejection in a MHC class II mismatched model.

UNLABELLED: Chronic rejection, or cardiac allograft vasculopathy (CAV), remains the leading cause of late death in heart transplant recipients. The precise role and contributions of T lymphocyte subsets to CAV development remains unknown. METHODS: Donor hearts from B6.C-H2bm12 mice were transplanted into T lymphocyte subset knockout recipients and T lymphocyte-reconstituted nude recipients. No immunosuppression was used. Intimal proliferation was measured morphometrically. In vitro studies were performed to analyze the donor-specific activation status of recipient CD8+ lymphocytes by examining cellular proliferation, interleukin-2 secretion, and interleukin-2Ralpha expression. Intracellular cytokine staining assay was performed to determine both the profile and source of intragraft cytokines. RESULTS: Hearts transplanted into wild-type recipients developed severe CAV by 24 days. Intimal lesions were absent in the hearts that were transplanted into nude and CD4-/- knockout mice (containing CD8+ lymphocytes). In contrast, the donor hearts in CD8-/- knockout recipients (containing CD4+ lymphocytes) developed CAV, but significantly less than in wildtype. Adoptive transfer of T lymphocyte subset populations into nude recipients confirmed that CAV was absolutely contingent on CD4+ lymphocytes, and that CD8+ lymphocytes played an additive role in intimal lesion progression in the presence of CD4+ lymphocytes. Although CD8+ lymphocytes alone did not cause CAV in vivo, we demonstrated that MHC class II disparate alloantigens activated CD8+ lymphocytes both in vivo and in vitro. Finally, both CD4+ and CD8+ lymphocytes contributed to the intragraft IL-2 and IFN-gamma production. CONCLUSIONS: In this MHC class II mismatched murine model, CAV is a T lymphocyte dependent event, and absolutely contingent on the presence of CD4+ lymphocytes. Furthermore, CD8+ lymphocytes (1) are activated by MHC class II disparate antigens and (2) play a significant role in the progression of lesion development. Finally, both CD4+ and CD8+ lymphocytes contribute to CAV development via secretion of IFN-gamma, a known mediator of CAV in this model.

Differential expression of RANTES chemokine, TGF-beta, and leukocyte phenotype in acute cellular rejection and quilty B lesions.

BACKGROUND: Because of the complexity of the trabeculated endocardial surface and tangential histologic sectioning, the differentiation of acute cellular rejection (ACR) from Quilty B lesions (QB) in endomyocardial biopsies (EMBs) is problematic. We hypothesized that the phenotype chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) expression of infiltrating cells and the pattern of expression of transforming growth factor-beta (TGF-beta) may distinguish ACR from QB. In previous studies, the number of RANTES-positive cells and the expression of TGF-beta correlated with the severity of rejection. METHODS: We used immunohistochemical techniques to stain sections of human EMBs with only QB (n = 14) or with only ACR (International Society for Heart and Lung Transplantation Grades 1A and 1B, n = 7; Grades 3A and 3B, n = 7) for B (CD20) and T-lymphocytes (CD3), macrophages (CD68), RANTES, and TGF-beta expression. We graded the percentage of positive cells from 0 to 4 (1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%, and 4 = 76% to 100%). RESULTS: When ACR was compared with QB, we found no difference in the proportion of myocardial B cells (0.9 +/- 0.3 vs 1.1 +/- 0.3, p = 0.17); however, we found a lesser proportion of T cells (1.8 +/- 0.5 vs. 2.8 +/- 0.9, p <0.01) but more macrophages (2.9 +/- 0.5 vs. 1.1 +/- 0.6, p < 0.0001) in ACR than in QB. We also found more RANTES-positive leukocytes in ACR vs. QB (2.8 +/- 1.3 vs. 1.9 +/- 0.9, p = 0.03). In QB, many endocardial vessels stained for TGF-beta (2.9 +/- 1.6). Myocardial vessels and injured myocytes in both ACR and QB expressed TGF-beta. CONCLUSIONS: In ACR, although T-lymphocytes are numerous, more than 50% of infiltrating cells are macrophages and more than 50% express RANTES. In QB lesions, more than 50% of infiltrating cells are T-lymphocytes and less that 50% of leukocytes will express RANTES. B cells are present in both ACR and QB, but on average comprise only 25% of the cells present. Thus, a relatively simple immunohistochemical analysis of endomyocardial biopsies may be useful in distinguishing ACR from QB.