C-reactive protein in the monitoring of acute rejection after heart transplantation

OBJECTIVE: To measure short duration sounds (L(PEAK)) in the neonatal intensive care unit and describe their intensity, incidence, and periodicity in relationship to activities within the unit. STUDY DESIGN: We measured 1-minute L(PEAK) at four locations within the intensive care unit, accumulating 48 hours of data for each weekday. RESULTS: Thirty-one percent of the L(PEAK) exceeded 90 dB. For further analysis, the data were transformed to the proportion exceeding 90 dB. These values varied significantly with day, week, location, and time of day. During physician rounds, there was a 16% relative increase in L(PEAK). CONCLUSION: These data demonstrate the intensity, incidence, and periodicity of short duration sounds in the intensive care nursery. Short duration sounds are known to affect the infant's physiological and behavioral states and should be addressed in future recommendations for sound control and reduction strategies.     

Treatment of humoral rejection after heart transplantation

BACKGROUND: Until a few years ago, the incidence of humoral rejection after heart transplantation was underestimated. These episodes were frequently very aggressive and often fatal, because the maintenance and emergency immunosuppression available at the time only inadequately covered the humoral branch of the immune response. In spite of individual case reports, the effects of blood purification procedures or cyclophosphamide in this situation can only be insufficiently estimated. METHODS: To evaluate this therapy concept, 20 dog-lymphocyte-antigen-matched dogs underwent heterotopic neck-heart transplantation. Fourteen dogs underwent transplantation after having been previously sensitized through multiple skin transplantations, 6 dogs were not sensitized (control). The animals received an induction with 3x 250 mg prednisolone, as well as triple immunosuppression (cyclosporine, azathioprine, and cortisone). Biopsy (light microscopy, immunofluorescence), intramyocardial voltage, electric myocardial impedance (>200 kHz, <10 kHz), and echocardiographic (left ventricular wall thickness, diastolic relaxation velocity) examinations were performed daily to monitor rejection. Rejection therapy was continued for 3 days according to the following regimen: apheresis, cortisone boluses (CB), and cyclophosphamide in group A1 (n = 4), apheresis and CB without cyclophosphamide in group A2 (n = 4), and CB only in group C (n = 6). The subsequent course under triple immunosuppression was then observed. RESULTS: In the sensitized animals the onset of severe humoral rejection on the fifth day deteriorated cardiac function down to 75% (70% to 80%) of the initial values. In groups A1 and A2, apheresis resulted in recovery to near-control values (89% to 94%) within two hours, and indeed to complete recovery (97% to 101%) after the second apheresis, that is, within 1 day. In group C recovery was delayed (2 days) and incomplete (84% to 91 %). After therapy was discontinued, rejection-related functional deterioration recurred immediately in group C, and from 2 to 3 days after apheresis, regardless of whether cyclophosphamide therapy was performed (group A1) or not (group A2). In the control group all animals showed a rejection-free posttransplantation course. CONCLUSIONS: By diluting inflammatory mediators, apheresis leads to a rapid improvement in cardiac function during severe humoral rejection after head transplantation. Neither apheresis nor cyclophosphamide therapy are able to have an immediate positive influence on the activation of the immune cascade and to prevent an ongoing rejection.     

Heart rate variability as an assessment of acute rejection after heart transplantation

BACKGROUND: Orthotopic heart transplantation is currently a widely accepted treatment for end-stage heart disease. Early detection and adequate therapy of acute rejection increases the survival rate. Currently, the most reliable technique for the detection of acute cardiac rejection (ACR) is endomyocardial biopsy (EMB), which is an invasive procedure with some intrinsic problems. The purpose of this study was to assess heart rate variability (HRV) as a noninvasive procedure for frequent monitoring of ACR. METHODS: Six consecutive orthotopic cardiac transplant recipients were prospectively recruited into this study. The follow-up periods ranged from seven to 359 days (median; 146 days). A precordial electrocardiograph (ECG) of 288 seconds was recorded at 5:00 PM before the patient underwent EMB. The results from the frequency domain analysis of the ECG signals were evaluated to correlate with the findings from EMB. RESULTS: Of 48 EMBs, 42 (87.5%) showed no evidence of rejection, four showed mild focal ACR (EMB grade 1A), one mild diffuse ACR (1B) and one moderate plurifocal ACR (3A). There was no moderate focal ACR (2), severe diffuse ACR (3B) or severe ACR (4). Correlation between ACR (3A) and a significant increase in HRV with a corresponding 'broad-band' or bell-shaped pattern on the power spectrum was noted. CONCLUSIONS: Our study in consecutive cardiac transplant recipients indicates that the changes in HRV provide clinicians with a new concept for heart transplant monitoring. Further study is needed to verify clinical utility.     

The incidence, morbidity, and mortality of surgical procedures after orthotopic heart transplantation

OBJECTIVE: The authors present their experience with patients having undergone orthotopic heart transplantation (OHT) in whom surgical conditions subsequently developed that required operative intervention. The incidence, morbidity, and mortality of these procedures are reported. SUMMARY BACKGROUND DATA: Several studies have evaluated the management options of biliary tract disease after OHT. Multiple reports of patients having undergone OHT who subsequently underwent peripheral vascular reconstructions, plastic reconstructive, and thoracic procedures also have been published. METHODS: A chart review of 349 patients who underwent OHT between 1985 and 1996 was conducted to identify surgical procedures that were required in the post-transplant period. Their outcomes are reported. RESULTS: Of 349 patients who underwent OHT, conditions requiring 94 surgical procedures developed in 54 patients (15%). Biliary tract disease developed in 17 patients (5%) who required cholecystectomy, 2 of the 5 patients with acute cholecystitis died. Eight patients (2%) underwent orthopedic procedures with no operative mortality. Flap advancements for sternal wound infections were performed in five patients and four deaths occurred. Seventeen thoracic procedures were performed in 11 patients with an overall mortality of 45%. Twenty-one vascular procedures were performed on 17 patients with 1 delayed death due to a malignancy. Seven patients underwent procedures of the colon and rectum with no mortality. Seven patients underwent repair of inguinal or incisional hernias with no mortality. Various infections occurred with one resultant death after operative intervention. Six procedures were performed for diseases of the small intestine with no resultant mortalities. CONCLUSIONS: Patients having undergone OHT and chronic immunosuppression are at increased risk of having complications develop from infection. Acute cholecystitis and sternal wound infection caused an inordinate risk of complications and death. Malignancies developed in four patients who required surgical intervention. A heightened awareness of coexisting peripheral vascular disease in patients transplanted for ischemic cardiomyopathy should exist. Close screening before surgery and surveillance after surgery to identify risk factors for infection and vascular disease and to screen for malignancies are essential.     

Late acute rejection and subclinical noncompliance with cyclosporine therapy in heart transplant recipients

BACKGROUND: Although noncompliance with immunosuppressive medication is recognized as a critical behavioral risk factor for late acute rejection episodes and graft loss after transplantation, little is known about the degree of subclinical cyclosporine noncompliance, its associated risk for acute late rejection episodes (>1 year after transplantation), and its determinants in heart transplant recipients. METHODS: The convenience sample of this longitudinal study included 101 European heart transplant recipients (87 men and 14 women), with a median age of 56 (Q1 = 50, Q3 = 61) and a median posttransplantation status of 3 (range 1 to 6) years. Subclinical cyclosporine noncompliance was measured during a 3-month period with electronic event monitoring. Selected sociodemographic, behavioral, cognitive, emotional, health, and treatment-related determinants of medication noncompliance were measured by using instruments with established psychometric properties or by patient interviews. With the use of iterative partitioning methods of cluster analysis, including nonstandardized electronic event monitoring compliance parameters, patients were categorized by degree of subclinical cyclosporine noncompliance into a 3-cluster solution. RESULTS: Overall compliance was high, with a median medication taking compliance of 99.4%. The 3 derived clusters, that is, excellent compliers (84%), minor subclinical noncompliers (7%), and moderate subclinical noncompliers (9%), differed significantly by degree of subclinical noncompliance (p < .0001) and showed a 1.19%, 14.28%, and 22.22% incidence of late acute rejections (p = .01), respectively. The 3 groups also differed in terms of former medication noncompliance (p = .02), appointment noncompliance (p = .03), and perceived self-efficacy with medication taking (p = .04). CONCLUSIONS: Although in absolute numbers cyclosporine compliance in this sample was high, minor deviations from dosing schedule were associated with an increased risk for acute late rejection episodes. This suggests a pivotal role of patient compliance in successful long-term outcome after transplantation.     

Detection of acute rejection of heart transplantation by Doppler color imaging

Doppler tissue imaging is a new technique of measuring the velocities of myocardial wall motion. In order to assess its value in the diagnosis of acute rejection, the velocities of the interventricular septum and left ventricular posterior wall were measured in systole and early diastole in 34 cardiac transplant patients at the time of their endomyocardial biopsy, using an M mode left parasternal short axis view. During 40 episodes of acute rejection (26 mild and/or moderate, 10 sub-severe and 4 severe), the wall velocities decreased significantly (p < 0.001) both in the interventricular septum and endocardium of the posterior wall. Myocardial velocities were significantly slower in sub-severe or severe rejection than in mild or moderate rejection. The most sensitive criterion was the measurement of posterior wall endocardial velocity in early diastole, a decrease of 10% having a sensitivity of 92% whereas the sensitivity of usual Doppler echocardiographic parameters is only 73%. Acute rejection, even mild cases, can be diagnosed with excellent sensitivity by measuring myocardial velocities by Doppler tissue imaging. This technique has the advantage of being non-invasive, reproducible and reliable in the follow-up of cardiac transplant patients.     

Early death in dialysis patients: risk factors and impact on incidence and mortality rates

Patients who die within the first 90 days after beginning dialysis are not included in mortality rates and may be absent from incidence counts. To identify factors associated with mortality within 3 months of the initiation of dialysis for ESRD and to estimate the impact of early deaths on ESRD incidence and mortality rates, this study investigated 15,245 patients who began dialysis in Georgia, North Carolina, and South Carolina over a 5-yr period. Data were collected by dialysis facility staff and reported to an ESRD registry. Six percent of all new patients died within 90 days of dialysis initiation (32% of all deaths occurring in the first year of treatment). Characteristics independently associated with increased risk of early death included older age, white race, male gender, physical and nutritional impairment, smoking, and the presence of cancer, congestive heart failure, clinical depression, and history of myocardial infarction. Depending on race-gender group, age-adjusted mortality rates based on this cohort were underestimated by 3 to 12% when patients who died early were excluded. These results suggest that certain patient characteristics-some potentially modifiable-confer increased risk of early death, and that the systematic exclusion of patients who die early from the U.S. national registry substantially influences ESRD mortality rates.     

Perspectives of patients with terminal renal failure: quality of life and psychological adjustment before and in the first year after heart transplantation

This prospective study was designed to compare quality of life, life satisfaction, and subjective ratings of health before and at variable time intervals after heart transplantation (HTx). 175 patients were included between February 1994 and December 1997. Every six months before and 1 1/2, 3, 6, and 12 months after HTx, they received the following standardized and validated questionnaires: German SF 36, heart failure and specific transplant symptom list, global quality of life assessment, Munich life quality dimension list, expected/experienced life changes after HTx. Inclusion criteria were the acceptance of the patient on the waiting list for HTx, good command of the German language, and a minimum age of 18 years. During data evaluation, median (Me), mean (M), and standard deviation (SD) were created from individual parameters. Quality of life was rated as very poor by 84% of patients with congestive heart failure. Only 6 weeks after HTx, 74% rated their quality of life as significantly better. Before HTx 80% were very unsatisfied about their health status and 87% about physical performance. Six weeks after HTx, this parameter improved significantly and 76% were very satisfied about their health status and 50% about physical performance. While somatic changes expected before HTx corresponded well with experienced ones, psychological improvements were smaller than expected, but one year after HTx they were significant (before: M = 3.66; SD = 0.9; Range (R) = 3.78 vs 12 months postop: M = 4.61; SD = 0.6; R = 2.67; p < 0.05). Quality of life correlated before HTx best with subjectively rated health (r = 0.61, p < 0.01) and 6 months after with satisfaction about health status (r = 0.76, p < 0.01). Only in 25% were expected improvements fulfilled regarding sexual activity/satisfaction, professional situation, and recreational activities. 90% of post-transplant patients reported physical complaints, most by effects of immunsuppression, but were coping well. The study shows that already 6 weeks after successful HTx all quality of life parameters improved significantly. Despite some unfulfilled expectations and complaints, the postoperative life situation of HTx patients appeared significantly improved.     

Early and late airway complications after lung transplantation: incidence and management

BACKGROUND: Airway anastomosis complications continue to be a source of morbidity for lung transplant recipients. METHODS: This study analyzes incidence, treatment, and follow-up of airway anastomotic complications occurring in 127 consecutive lung transplant airway anastomoses (77 single lung and 25 bilateral sequential lung). Complications were categorized as stenosis (11), granulation tissue (8), infection (7), bronchomalacia (5), or dehiscence (3). Follow-up after treatment ranged from 6 months to 4 years. RESULTS: Nineteen airway anastomosis complications (15.0%) occurred in 18 patients. Telescoping the airway anastomosis reduced the complication rate to 12 of 97 (12.4%), compared with 7 of 30 (23.3%) for omental wrapping, (p = 0.15). Complications developed in 13 of 77 single-lung airway anastomoses (16.9%) versus 6 of 50 bilateral sequential lung recipients (12.0%). Treatment consisted of stenting (9 airway anastomoses), bronchodilation (8), laser debridement (4), rigid bronchoscopic debridement (2), operative revision (2), and growth factor application (2). There was no difference in actuarial survival between patients with or without airway anastomosis complications (p = 1.0). CONCLUSIONS: Airway anastomosis complications can be successfully managed in the immediate or late postoperative period with good outcome up to 4 years after intervention.