A clinical trial combining donor bone marrow infusion and heart transplantation: intermediate-term results.

BACKGROUND: Donor chimerism (the presence of donor cells of bone marrow origin) is present for years after transplantation in recipients of solid organs. In lung recipients, chimerism is associated with a lower incidence of chronic rejection. To augment donor chimerism with the aim to enhance graft acceptance and to reduce immunosuppression, we initiated a trial combining infusion of donor bone marrow with heart transplantation. Reported herein are the intermediate-term results of this ongoing trial. METHODS: Between September 1993 and August 1998, 28 patients received concurrent heart transplantation and infusion of donor bone marrow at 3.0 x 10(8) cells/kg (study group). Twenty-four contemporaneous heart recipients who did not receive bone marrow served as controls. All patients received an immunosuppressive regimen consisting of tacrolimus and steroids. RESULTS: Patient survival was similar between the study and control groups (86% and 87% at 3 years, respectively). However, the proportion of patients free from grade 3A rejection was higher in the study group (64% at 6 months) than in the control group (40%; P =.03). The prevalence of coronary artery disease was similar between the two groups (freedom from disease at 3 years was 78% in study patients and 69% in controls). Similar proportions of study (18%) and control (15%) patients exhibited in vitro evidence of donor-specific hyporesponsiveness. CONCLUSIONS: The infusion of donor bone marrow reduces the rate of acute rejection in heart recipients. Donor bone marrow may play an important role in strategies aiming to enhance the graft acceptance

A prospective trial of tacrolimus (FK 506) in clinical heart transplantation: Intermediate-term results

Between January 1, 1989, and December 31, 1994, we have treated 122 primary heart recipients with FK 506 (group I) and 121 with cyclosporine (group II). Fifty patients in the cyclosporine (CyA) group received no lympholytic induction (CyA alone) and 71 others received lympholytic induction with either rabbit antithymocyte globulin or OKT3 (CyA+LI). The mean follow-up was longer in the FK 506 group than in the CyA groups (3.2 ± 1.3 vs 2.3 ± 1.8 years; p < 0.01). Patient survival did not differ on the basis of the type of immunosuppression used. At 3 months after transplantation, the freedom from rejection in the FK 506 group was higher than that of the CyA-alone group (47% vs 22%, p < 0.01) but similar to that of the CyA+LI group (47% vs 53%). The linearized rejection rate (episodes/100 patient-days) of the FK 506 group (0.09 episodes) was lower (p < 0.05) than that of the CyA-alone group (0.26) and the CyA+LI group (0.13). The requirement for pulsed steroids to treat rejection was less in common in the FK 506 group than in either CyA group. Eighteen patients in the CyA group had refractory rejections; all resolved with FK 506 rescue. Two patients in the FK 506 group had refractory rejection that resolved with total lymphoid irradiation (n = 1) and methotrexate therapy (n = 1). Patients receiving FK 506 had a lower risk of hypertension and required a lower dose of steroids. Although the mean serum creatinine concentration at 1 year was higher in the FK 506 group, this difference disappeared after 2 years. No patients required discontinuation of FK 506 because of its side effects. Our intermediate-term results indicate that FK 506 compares favorably with CyA as a primary immunosuppressant in heart transplantation

On-line estimation of changes in left ventricular stroke volume by transesophageal echpcardiographic automated border detection in patients undergoing coronary artery bypass grafting

Echocardiographic automated border detection can determine the interface between blood and myocardial tissue and calculate left ventricular (LV) cavity area in real-time. The objective was to determine if on-line measurements of LV cavity area by transesophageal automated border detection could be used to determine beat-to-beat changes in stroke volume in humans. Studies were attempted on 9 consecutive patients, aged 66 ± 8 years, undergoing coronary bypass surgery. Stroke volume was measured by electromagnetic flow from the ascending aorta, and LV cavity area was measured at the midventricular short-axis level. Simultaneous area and flow data were recorded on a computer workstation through a customized interface with the ultrasound system. Recordings were performed during baseline apnea and rapid alterations induced by inferior vena caval occlusions before and after cardiopulmonary bypass. Measurements of stroke area (maximal area-minimal area) were correlated with stroke volume for matched beats. Data were available for analysis on 8 of 9 patients before and on 5 patients after cardiopulmonary bypass for 644 beats. Stroke area was closely correlated with stroke volume both before (mean R = 0.94 ± 0.03, SEE = 0.33 ± 0.12 cm2) and after (mean R = 0.92 ± 0.05, SEE = 0.59 ± 0.81 cm2) cardiopulmonary bypass. The slopes of these stroke area-stroke volume relations were quite reproducible from before to after cardiopulmonary bypass in the same patient but varied between individual patients. Transesophageal automated border detection has potential for on-line estimation of changes in stroke volume in selected patients. © 1993

Changes in electrocardiographic morphology reflect instantaneous changes in left ventricular volume and output in cardiac surgery patients

We examined the relation between changes in R-to-T wave amplitude ratios (R:T) and left ventricular (LV) performance as cardiac output was rapidly varied by inferior vena caval occlusion in 6 subjects prior to cardiopulmonary bypass. To assess the influence of contractility, paired studies before and after bypass were performed in 4 subjects. Stroke volume and cardiac output were assessed by aortic flow probe, and transesophageal echocardiographic LV area measures using the automated border-detection method were used to give LV stroke area, stroke force, maximal LV area, fractional area change, end-systolic elastance, and preload recruitable stroke force. Data were collected on computer and analyzed by linear regression. Significant changes in R:T and measured LV variables during the inferior vena caval occlusion were stroke volume (r = 0.81), LV stroke area (r = 0.77), LV stroke force (r = 0.81), maximal LV area (r = 0.78), and cardiac output (r = 0.80). However, R:T varied inconsistently in relation to fractional area change. After cardiopulmonary bypass, the linear relation between R:T with LV stroke force, LV stroke volume, and maximal LV area persisted, but at a lesser slope. Although absolute pre-inferior vena caval occlusion R:T did not correlate with end-systolic elastance or preload recruitable stroke force, the change in the slope of these linear relations correlated well with the change in end-systolic elastance after surgery (r = 0.92). Instantaneous changes in electrocardiographic morphology reflect changes in LV preload-dependent variables, whereas long-term changes in electrocardiographic morphology may also reflect changes in contractile state. © 1995

Rapid estimation of left ventricular contractility from end-systolic relations by echocardiographic automated border detection and femoral arterial pressure

Background: Automated echocardiographic measures of left ventricular (LV) cavity area are closely correlated with changes in volume and can be coupled with LV pressure to construct pressure-area loops in real time. The objective was to rapidly estimate LV contractility from the end-systolic relations of cavity area (as a surrogate for LV volume) and femoral arterial pressure (as a surrogate for LV pressure) in patients undergoing cardiac surgery. Methods: Studies were attempted on 18 consecutive patients with recordings of LV pressure, LV area, and femoral arterial pressure on a computer workstation interfaced with the ultrasound system. End-systolic pressure-area relations (in terms of pressure-area elastance [E'(es)]) from pressure-area loops during inferior vena caval occlusions were determined before and immediately after cardiopulmonary bypass using both LV and arterial pressure by semiautomated and automated iterative linear regression methods. Results: Data sets were available for 13 patients before and 8 patients after bypass (21 studies in 14 patients). E'(es) by arterial pressure was closely correlated with E'(es) by LV pressure: r = 0.96, standard error of the estimate = 2 mmHg/cm2, y = 1.01 x -0.7 by the semiautomated method and r = 0.94, standard error of the estimate = 3 mmHg/cm2, y = 1.02 x -0.5 by the automated method. Analysis of semiautomated and automated estimates of E'(es) from arterial pressure and E'(es) using LV pressure by the Bland-Altman method showed no systematic measurement bias and calculated limits of agreement of 8 and 9 mmHg/cm2, respectively. Similar decreases in E'(es) by arterial and LV pressure occurred from before to after bypass in 7 patients with paired data sets: 32 ± 12 to 15 ± 6 mmHg/cm2 and 32 ± 15 to 15 ± 7 mmHg/cm2, respectively (P < 0.05 for both). Conclusions: On-line femoral arterial pressure and LV area data by echocardiographic automated border detection may be used to rapidly calculate E'(es) as a means to estimate LV contractility in selected patients