Report from a forum on US heart allocation policy.

Since the latest revision in US heart allocation policy (2006), the landscape and volume of transplant waitlists have changed considerably. Advances in mechanical circulatory support (MCS) prolong survival, but Status 1A mortality remains high. Several patient subgroups may be disadvantaged by current listing criteria and geographical disparity remains in waitlist time. This forum on US heart allocation policy was organized to discuss these issues and highlight concepts for consideration in the policy development process. A 25-question survey on heart allocation policy was conducted. Among attendees/respondents were 84 participants with clinical/published experience in heart transplant representing 51 US transplant centers, and OPTN/UNOS and SRTR representatives. The survey results and forum discussions demonstrated very strong interest in change to a further-tiered system, accounting for disadvantaged subgroups and lowering use of exceptions. However, a heart allocation score is not yet viable due to the long-term viability of variables (used in the score) in an ever-developing field. There is strong interest in more refined prioritization of patients with MCS complications, highly sensitized patients and those with severe arrhythmias or restrictive physiology. There is also strong interest in distribution by geographic boundaries modified according to population. Differences of opinion exist between small and large centers.

Feasibility of a Composite Measure of Pulmonary Vascular Impedance and Application to Patients with Chronic RV Failure Post LVAD Implant.

Pulmonary vascular impedance (PVZ) describes RV afterload in the frequency domain and has not been studied extensively in LVAD patients. We sought to determine (1) feasibility of calculating a composite (c)PVZ using standard of care (SoC), asynchronous, pulmonary artery pressure (PAP) and flow (PAQ) waveforms; and (2) if chronic right ventricular failure (RVF) post-LVAD implant was associated with changes in perioperative cPVZ.PAP and PAQ were obtained via SoC procedures at three landmarks: T(1), Retrospectively, pre-operative with patient conscious; and T(2) and T(3), prospectively with patient anesthetized, and either pre-sternotomy or chest open with LVAD, respectively. Additional PAP's were taken at T(4), following chest closure; and T(5), 4-24 h post chest closure. Harmonics (z) were calculated by Fast Fourier Transform (FFT) with cPVZ(z) = FFT(PAP)/FFT(PAQ). Total pulmonary resistance Z(0); characteristic impedance Zc, mean of cPVZ(2-4); and vascular stiffness PVS, sum of cPVZ(1,2), were compared at T(1,2,3) between +/-RVF groups.Out of 51 patients, nine experienced RVF. Standard hemodynamics and changes in cPVZ-derived parameters were not significant between groups at any T.In conclusion, cPVZ calculated from SoC measures is possible. Although data that could be obtained were limited it suggests no difference in RV afterload for RVF patients post-implant. If confirmed in larger studies, focus should be placed on cardiac function in these subjects.

Predictors and outcomes of health-related quality of life in caregivers of cardiothoracic transplant recipients.

Cardiothoracic transplant programs generally require that transplant recipients have family caregivers to assist them posttransplant. The burden of caregiving on the family members remains poorly understood. If caregivers' well-being is compromised by caregiving, it may bode poorly for transplant recipients' own health in the long-term posttransplant. We examined caregiver health-related quality of life (HRQOL) during the first year after their family member's transplant, its predictors and its relationship to subsequent patient survival. Adult (aged 18+) caregivers of 242 cardiothoracic transplant recipients (lung = 134; heart = 108) completed assessments of demographics, psychosocial characteristics and caregiver burden at 2 months posttransplant, and HRQOL at 2, 7 and 12 months posttransplant. Recipients' survival time was obtained from medical records. Caregiver HRQOL was generally high across the first-year posttransplant in emotional and social functioning; caregiver physical functioning significantly worsened. There were no differences by type of recipient transplant. Greater caregiver burden predicted poorer caregiver HRQOL in several physical domains at 12 months posttransplant. Transplant recipients whose caregivers had lower perceived general health at 12 months posttransplant showed poorer survival rates during the subsequent 7 years of follow up. Transplant teams should identify those caregivers at risk for poorer general health posttransplant to maximize positive outcomes for the entire family.

Alemtuzumab induction prior to cardiac transplantation with lower intensity maintenance immunosuppression: one-year outcomes.

Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1-3 (8.5 vs. 12.9), month 4-6 (10.2 vs. 13.0), month 7-9 (10.2 vs. 11.9) and month 10-12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids.

Hemodynamics and the vascular endothelial cytoskeleton.

Although there is considerable evidence to suggest that hemodynamics play an important role in vascular disease processes, the exact mechanisms are unknown. With this in mind, we have designed a pulsatile perfusion apparatus which reproducibly delivers pulsatile hemodynamics upon freshly excised canine carotid arteries in vitro. Quantifiable simulations included normotension with normal or lowered flow rates (120/80 mmHg, 120 and 40 ml/min), normotension with lowered or elevated transmural pressures (40-170 mmHg), and elevated pulse pressure (120 and 80 mmHg) with normal (150 ml/min) or elevated rates of flow (300 and 270 ml/min). Arterial biomechanical stresses and cellular behaviors were characterized biochemically and morphologically under all these stimulations which continued for 2-24 h. We found that increased pulse pressure alone had little effect on the total amount of radiolabeled [4-14C]cholesterol present within the medial compartment. However, normotension when coupled with altered transmural pressure yielded a three- to fourfold increase. Combinations of increased pulse pressure and flow potentiated cholesterol uptake by a factor of 10 when compared with normotension control values. Simulations that enhanced carotid arterial cholesterol uptake also influenced the endothelial cytoskeletal array of actin. Stress fibers were not present within the carotid endothelial cells of either the sham controls or the normotension and increased pulse pressure (normal flow) simulations. Endothelial cells lining carotids exposed to elevations in flow or those present within vessels perfused as per simulation b above assembled stress fibers (x = 4 and 10 per cell, respectively) within the time course of these studies. When endothelial cells were subjected to hemodynamic conditions that potentiated maximally cholesterol transport, no diffuse or stress fiber staining could be seen, but the cortical array of actin was intact. These results suggest that those biomechanical stresses that alter endothelial permeability and intimal integrity may do so via cytoskeletal actin signaling.

Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices.

BACKGROUND: Left ventricular assist device (LVAD) support of the failing heart induces salutary changes in myocardial structure and function. Matrix metalloproteinases (MMPs) are increased in the failing heart and are induced by stretch in cardiac cells in vitro. We hypothesized that mechanical unloading may affect LV plasticity by regulating MMPs and their substrates. METHODS AND RESULTS: LV samples were collected from patients with dilated cardiomyopathy (DCM, n=14) or ischemic cardiomyopathy (ICM, n=16) at the time of implantation of the LVAD and again during cardiac transplantation. MMP-1, -3, and -9 were measured by ELISA, MMP-2 and -9 gelatinolytic activity by gelatin zymography, and tissue inhibitors of metalloproteinases (TIMPs) by Western blot. Total soluble and insoluble collagens were separated by pepsin solubilization, and the contents were determined by quantification of hydroxyproline. The undenatured soluble collagen was measured by Sircol collagen assay. The results showed that MMP-1 and -9 were decreased, whereas TIMP-1 and -3 were increased, but there was no change in MMP-2 and -3 and TIMP-2 and -4 after LVAD support. The undenatured collagen was increased, with the ratio of undenatured to total soluble collagens increased in ICM and that of insoluble to total soluble collagens increased in DCM after LVAD support. CONCLUSIONS: The reduced MMPs and increased TIMPs and ratios of undenatured to total soluble collagens and insoluble to total soluble collagens after LVAD support suggest that reduced MMP activity diminished damage to the matrix. These changes may contribute to the functional recovery and LV plasticity after LVAD support.

Cardiac rhythm disturbances early after orthotopic heart transplantation: prevalence and clinical importance of the observed abnormalities.

To precisely define the incidence, type and consequences of cardiac arrhythmias early after heart transplantation, 25 cardiac transplant recipients were monitored continuously for 728 days from the day of surgery to discharge or death. A subset of 15 patients had sinus node function studies with overdrive suppression performed weekly at the time of endomyocardial biopsy. Results revealed sinus bradycardia in 10 patients (40%) and junctional bradycardia in 6 (24%). Supraventricular tachycardia in the form of atrial tachycardia, atrial fibrillation and atrial flutter occurred in 11 patients (44%). Ventricular tachycardia occurred in 15 patients (60%) and was nonsustained in all. Cardiac pacing for 1,403 h was used in nine patients with a pulse rate less than 50 beats/min; seven recovered and permanent pacing was instituted in two. In the subgroup that had sinus node function studies, seven patients were identified with clinical bradyarrhythmia; each had abnormal sinus node recovery time (greater than 1,400 ms) and abnormal corrected sinus node recovery time (greater than 525 ms) in at least one study. These seven patients also had a significantly prolonged ischemic time (236 +/- 26 versus 159 +/- 68 min, p less than 0.01). In conclusion, cardiac arrhythmias, particularly ventricular tachycardia and bradyarrhythmia, occur more commonly early after orthotopic heart transplantation than has previously been reported. Sinus node dysfunction due to prolonged organ ischemic time, antiarrhythmic drug use or surgical trauma, alone or in combination, may contribute to these arrhythmias.

Resolution of severe pulmonary hypertension after heterotopic cardiac transplantation.

In patients with severe congestive heart failure, a marked elevation in pulmonary vascular resistance limits the success of orthotopic cardiac transplantation, thus providing the rationale for heterotopic transplantation. To determine the changes in pulmonary hemodynamics after heterotopic cardiac transplantation, postoperative right heart pressures were serially measured in five patients who underwent this operation for end-stage congestive heart failure accompanied by severe secondary pulmonary hypertension and elevation in calculated pulmonary vascular resistance. Hemodynamics were compared with those of a matched group of 10 orthotopic cardiac transplant recipients. Preoperatively, pulmonary artery mean and wedge pressures, pulmonary vascular resistance and transpulmonary pressure gradient (pulmonary artery mean minus wedge pressure) were significantly higher in the heterotopic group. Postoperatively, significant improvement in pulmonary hemodynamics occurred in both groups and, by 12 months, the pulmonary artery mean pressure, wedge pressure, pulmonary vascular resistance and transpulmonary pressure gradient were similar in the two groups. These findings suggest that pulmonary hypertension secondary to congestive heart failure, even when severe and associated with a high pulmonary vascular resistance, is to a great extent reversible.

In vitro studies of endomyocardial biopsies from heart transplant recipients on RATG and OKT3 immunoprophylaxis protocols.

Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive T lymphocytes were analyzed in cardiac transplant patients on RATG (n = 24) and OKT3 (n = 9) immunoprophylaxis protocols. During the first three months posttransplant, 27% of the 167 biopsies in the RATG group showed histological grades of 2 or higher, significantly less than the 44% frequency of positive histology for biopsies in the OKT3 group (P = 0.035). For the histologically positive biopsies the frequency of lymphocyte growth, and the primed lymphocyte testing (PLT)* and CML activity of biopsy grown cells were similar in the RATG and OKT3 groups. However, for histologically negative biopsies, there was significantly more lymphocyte growth in the OKT3 than in the RATG groups (68% vs. 30%; P = 0.005). There was also significantly greater donor-specific CML activity of the biopsy-grown cultures in the OKT3 group. These data that suggest less cellular rejection is associated with RATG than with OKT3 immunoprophylaxis. They extend our previously reported clinical experience of a higher rejection-free survival in patients on the RATG protocol.

Histocompatibility and other risk factors for histological rejection of human cardiac allografts during the first three months following transplantation.

A histological analysis of 2564 endomyocardial biopsies was conducted in 349 cardiac transplant patients to determine potential risk factors for acute cellular rejection during the first three months following transplantation. This analysis dealt with the frequency, time of onset, and duration of cellular rejection. Patients on perioperative RATG experienced significantly less rejection than patients on OKT3 or without antilymphocyte antibody immunoprophylaxis. A trend was noted toward increased rejection in recipients diagnosed originally with chronic myocarditis compared with patients in other disease categories including ischemic heart disease and dilated cardiomyopathy. No significant differences were seen in histological rejection between male and female recipients. On the other hand, patients over 55 years of age were found at lower risk of histological rejection. The results of this analysis have demonstrated quite clearly, but not unexpectedly, that a greater degree of HLA mismatching correlates with increased cellular rejection. This effect was noted not only for the HLA-A,B and DR antigens, but also HLA-DQ and HLA-DRw52/53 antigens. In multivariate analysis, the highest level of statistical significance was obtained for the combined HLA-A,B,DR and DQ group. Sensitized patients with panel-reactive lymphocytotoxic antibodies of greater than 10% experienced more histological rejection than nonsensitized patients. On the other hand, a positive lymphocytotoxic crossmatch did not appear to influence cellular rejection of cardiac allografts. Also, no differences were seen in histological rejection between ABO-identical and compatible heart transplants. These findings further support the concept that donor HLA compatibility and pretransplant sensitization represent significant risk factors for cellular rejection in cardiac transplantation.

Propagation of alloreactive lymphocytes from histologically negative endomyocardial biopsies from heart transplant patients. Association with subsequent histological evidence of allograft rejection.

Endomyocardial biopsies from heart transplant patients were cultured in vitro in the presence of Interleukin-2 and irradiated feeder cells to propagate graft-infiltrating lymphocytes. A correlation was seen between the frequency of lymphocyte growth and the degree of cellular infiltration of the biopsies. In this study, 43 of 113 (38%) histologically negative biopsies obtained from 55 patients during the first month post-transplant yielded lymphocyte cultures. The cumulative incidence of subsequent histological rejection was considerably higher in patients with such "grower" biopsies than in patients with "nongrower" biopsies. In the grower group, we were able to obtain data on alloreactivity of 32 lymphocyte cultures assayed by primed lymphocyte testing (PLT). The presence of donor-specific PLT reactivity in the cultured lymphocytes was associated with an additional risk for subsequent histological rejection. These findings suggest that the in vitro culturing of histologically negative endomyocardial biopsies will identify patients at increased risk for developing heart transplant rejection.

Cardiac transplantation in survivors of lymphoma: a multi-institutional survey.

BACKGROUND: Cardiac transplantation has been successfully performed in patients with a history of presumably cured Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Though the risk of recurrence is a major concern, the long-term influence of prior cancer and cancer therapy on posttransplant outcome has not been previously investigated. METHODS: Questionnaires were sent to 130 cardiac transplant centers in the United States registered with the United Network for Organ Sharing. Data collected included patient demographics; type, stage, and timing of HD/NHL; treatment for HD/NHL; posttransplant immunosuppressive regimen, rejection history, and outcomes; and Epstein-Barr virus status. RESULTS: Thirty-four cardiac transplant recipients with a previous history of HD (n=16) or NHL (n=18) were identified. HD patients averaged 41+/-15 years of age, with a mean disease-free interval of 15+/-9 years at the time of transplantation. NHL patients averaged 42+/-17 years of age with a mean disease-free interval of 10+/-9 years at the time of transplantation. The mean follow-up for the entire group was 50 months (range, 2 days to 136 months), and mean follow-up for the survivors was 67 months (range, 23-136 months). The 1-, 3-, 5-, 7-, and 10-year actuarial survival estimates for the entire group are 77%, 64%, 64%, 64%, and 50%, respectively. Actuarial survival was lower in HD patients (P=0.04) and in patients who had previously undergone splenectomy (P=0.008). Cox regression analysis identified only prior splenectomy (P=0.02) as an independent risk factor for mortality after cardiac transplantation with an adjusted relative risk of 6.2 (1.7-21.9, 95% confidence intervals). CONCLUSIONS: Although the numbers are small, these data strongly suggest that there is an increased mortality risk for cardiac transplant recipients with prior HD who have undergone splenectomy.

Does transplantation produce quality of life benefits? A quantitative analysis of the literature.

BACKGROUND: Despite numerous reports published since the early 1970s, it is frequently asserted that quality of life (QOL) outcomes of transplantation have seldom been investigated and/or that little is known about QOL. This view may have persisted due to lack of adequate cumulation and synthesis of existing data. We performed an exhaustive, quantitative literature review to determine the nature and degree of any QOL benefits associated with transplantation in adults. METHODS: All independent, peer-reviewed empirical, English-language QOL studies were retrieved for six areas of transplantation: kidney, pancreas/combined kidney-pancreas, heart, lung/combined heart-lung, liver, and bone marrow. Studies' findings were analyzed to determine whether the weight of evidence suggested that (a) QOL improved from pre- to posttransplant, (b) transplant recipient QOL was better than that of patient comparison groups, and (c) recipient QOL equaled that of healthy nonpatient samples. RESULTS: A total of 218 independent studies, evaluating a total of approximately 14,750 patients, were identified. The majority of studies demonstrated statistically significant (P<0.05) pre- to posttransplant improvements in physical functional QOL, mental health/cognitive status, social functioning, and overall QOL perceptions. The majority documented physical functional and global QOL advantages for transplant recipients relative to ill comparison groups. The studies did not indicate that recipient QOL in specific functional areas equaled that of healthy, nonpatient cohorts, although global QOL perceptions were often high. CONCLUSIONS: Although transplantation may not restore to the patient the "normal" life he/she may once have had, convergent evidence from six areas of transplantation, a variety of study designs, and demographically diverse study cohorts suggests that there are distinct QOL benefits of transplantation. Future work is required to identify background and personal factors that influence the degree of QOL benefits that any individual patient realizes from transplantation.

Cyclosporine nephrotoxicity in cardiac allograft patients--a seven-year follow-up.

Renal function was observed retrospectively in a population of 228 adults who underwent a cardiac allograft at the University of Pittsburgh from June 1980 through June 1987, survived a minimum of one year, and received cyclosporine. Renal function was determined by serial measurement of serum creatinine concentration. Serum creatinine rose from 1.2 +/- 0.0 mg/dl at time of hospital discharge to 2.0 +/- 0.0 mg/dl at two and four years and 3.3 +/- 0.1 mg/dl at seven years. The fall in renal function was biphasic, with a rapid decline (reciprocal creatinine slope -0.018 dl/mg-mo) through 24 months and a slower decline thereafter -0.0036 dl/mg/month). This occurred despite a progressive decrease in cyclosporine levels from 668 +/- 23 ng/ml (whole blood RIA) to 380 +/- 12 ng/ml at seven years. Three of 222 patients (1.6%) developed end-stage renal disease within 18 months of initiation of cyclosporine therapy. Only one additional patient of 26 followed through 54 months (3.8%) developed end-stage disease thereafter. The decline in renal function seen with cyclosporine is rapid in the first 18 months, with a slower but continuing decline seen with later follow up. At least in heart transplantation, the risk of end-stage renal disease is significant, but not prohibitive.

Heart transplantation in diabetic recipients.

Preexisting diabetes mellitus (DM) has been regarded as a contraindication to heart transplantation (HT). This prejudice has been based upon concern over increased infection rates and worsening DM with the initiation of prednisone immunosuppression. To better evaluate these suppositions, we reviewed our experience with diabetic patients who underwent HT. Between 6/80 and 1/88, 367 nondiabetics (NDs) and 19 diabetics underwent HT at our institution. Of the 19 diabetic recipients (DRs), two were black and four were female. Six DRs were on insulin (average daily dose: 46 U) prior to HT, and the remainder required oral hypoglycemic agents. Following HT, five DRs had insulin substituted for oral hypoglycemics. The 11 insulin-dependent DRs now require an average daily dose of 48 U. The average duration of follow-up for the 19 DRs was 17 months (range 1-67 months). During this time, 5 hospitalizations were required for complications of diabetes. The rejection rate was not higher for the DRs than the NDs (0.37 events/100 pt. days vs. 0.51 events/100 pt. days). The DRs who have undergone coronary angiography up to 4 years following HT have had no evidence of coronary atherosclerosis. Three-year survival for DRs and NDs is similar. DRs have a slightly higher incidence of lethal infections than NDs, which is not statistically significant (16% at 17 months vs. 10% (p greater than 0.4). We conclude that carefully selected diabetics can undergo HT with minimal consequent worsening of their DM. Diabetic HT recipients do not suffer a higher incidence of graft atherosclerosis, rejection, or lethal infection.

Proliferative responses of bronchoalveolar lavage lymphocytes from heart-lung transplant patients.

Donor-specific alloreactivity of bronchoalveolar lavage (BAL) lymphocytes was evaluated in the immunologic monitoring of lung transplant patients. The study dealt with 161 BAL performed on 28 transplant recipients. Unseparated BAL cells, separated BAL lymphocytes, and PBL were tested for donor-specific proliferative responses in 3-day primed lymphocyte testing (PLT), and for nonspecific proliferative responsiveness to exogenous IL-2. The proliferation data were analyzed for correlation with the status of the lung allograft assessed clinically, histologically, and by pulmonary function testing. Positive PLT responses of BAL lymphocytes were observed in 20 of 22 acute rejection episodes (91%) and in 24 of 35 cases (69%) when chronic rejection was diagnosed. During clinical quiescence donor-specific proliferative activity was demonstrated in only 4 of 35 cases (11%). Thus, acute rejection and chronic rejection correlated significantly (P less than 0.001) with donor-specific PLT reactivity of BAL lymphocytes. Though significant association with rejection was observed for the alloreactivity of unseparated BAL cells and PBL, the sensitivity of the PLT test with these cells was significantly lower than that with BAL lymphocytes. Similarly, the IL-2 proliferative activity of BAL lymphocytes was significantly increased during acute and chronic rejection. However, this test had lower sensitivity and specificity than did the donor-specific PLT. These findings suggest the usefulness of the donor-specific PLT of BAL lymphocytes as a reliable method for monitoring pulmonary rejection.

Optimal perioperative immunosuppression in cardiac transplantation using rabbit antithymocyte globulin.

A randomized trial of RATG (polyclonal) vs. OKT3 (monoclonal) antibody prophylaxis was carried out in 82 cardiac transplant recipients who, in addition, received baseline immunosuppression with cyclosporine, azathioprine and prednisone. One-year actuarial survival was comparable between groups (95% and 98%). The incidence of moderate or severe rejection within the first 30 days of transplant was over 7 times greater in patients receiving OKT3 vs. those receiving RATG. Patients receiving OKT3 were more likely to have repeated episodes of rejection and the mean time to rejection for patients receiving OKT3 was shorter (33 days) than for RATG patients (67 days). At 120 days, 52% of RATG patients were free of rejection while only 37% of the OKT3 patients were rejection-free. There was no difference in the incidence of major or minor bacterial or viral infection between groups. Patients receiving OKT3 showed a less-prolonged depression of the CD3 and CD4 T cell subsets than did those receiving RATG. Significant hemodynamic side-effects were seen after the first dose of OKT3 and there was a 5% incidence of aseptic meningitis associated with its use.

Circulating interleukin-6 in severe heart failure.

In a group of patients with New York Heart Association class IV heart failure, significant relations between interleukin-6 and tumor necrosis factor-alpha, and between levels of both interleukin-6 and tumor necrosis factor-alpha and plasma levels of norepinephrine were observed. The present study also demonstrates that in patients with heart failure, elevated levels of tumor necrosis factor-alpha and interleukin-6 may be present even without cachexia.

Effects of acute alterations in left ventricular loading conditions on peak filling rate in the denervated (transplanted) ventricle.

Peak filling rate is an indicator of left ventricular (LV) diastolic function. It is influenced by heart rate, loading conditions, sympathetic nervous system activity, ejection fraction and other factors. To determine the effect of altered loading conditions on peak filling rate, independent of heart rate and sympathetic nervous system activity, 12 patients were studied 3 weeks after orthotopic heart transplantation. Plasma catecholamine level, heart rate and ejection fraction were not changed by any maneuver. Nitroglycerin caused a decrease in pulmonary artery wedge pressure (9 +/- 2 to 6 +/- 1 mm Hg, p less than 0.001) and in absolute peak filling rate (46.0 +/- 3.0 to 42.8 +/- 2.5 kcts/s, p less than 0.01), but no change in normalized peak filling rate. Volume infusion increased pulmonary artery wedge pressure (9 +/- 2 to 12 +/- 2 mm Hg, p less than 0.001) and absolute peak filling rate (46.0 +/- 3.0 to 51.5 +/- 5.3 kcts/s, p less than 0.01), but peak filling rate normalized to stroke volume was unchanged. During nitroglycerin and volume infusions, there was a high correlation between changes in pulmonary artery wedge pressure and absolute peak filling rate (r = 0.82, p less than 0.001). With normalization of peak filling rate, these variables correlated less well. With methoxamine, 4 patients demonstrating systolic dysfunction had a decrease in absolute and normalized peak filling rate despite a large increase in pulmonary artery wedge pressure. The other 8 patients without systolic dysfunction had an increase in pulmonary artery wedge pressure with increased absolute but unchanged normalized peak filling rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Propagation of infiltrating lymphocytes and graft coronary disease in cardiac transplant recipients.

The pattern of lymphocyte growth from endomyocardial biopsies in 55 heart transplant recipients was shown to be correlated with the subsequent development of graft coronary disease. Persistent lymphocyte growth was observed in 39 patients, and 15 of these growers (or 41%) developed graft coronary disease. In contrast, only 1 of 15 patients (or 6%) with nongrower biopsies showed subsequent graft coronary disease. Thus, biopsy growth was associated with a higher incidence of subsequent GCD (p = 0.02). A comparison between the group of 15 growers with subsequent graft coronary disease and the 24 growers without subsequent graft coronary disease did not show any differences with respect to patient age, presence of coronary artery disease in the native heart, biopsy histology, donor alloreactivity of biopsy grown lymphocytes, and immunosuppressive drug regimen. On the other hand, the number of treated rejection episodes was significantly lower in the grower group with subsequent graft coronary disease (p = 0.04). These data support the concept that graft coronary disease may involve rejection and that more immunosuppression may lower its incidence. This concept is strengthened by findings showing that alloreactive T cells can be propagated from coronary arteries of cardiac allografts with graft coronary disease.