Transmission of sarcoidosis via cardiac transplantation.
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Cardiomyopathies↗
Biomedical subjects
A Keogh
Publications and source records attributed to A Keogh.
Recurrent autoimmune LKM hepatitis with multiple relapses.
We describe three females who since childhood and puberty have presented with several relapsing episodes of acute or chronic LKM positive hepatitis. Many episodes resolved spontaneously with recovery of normal liver function, although treatment with steroids, steroids/azathioprine was used at occasions. No clear pattern of precipitating factors has emerged though in some cases possible temporal relationship of episodes to menarche, oral contraceptives use or pregnancy has suggested a role for female sex hormones. We discuss briefly the possible mechanisms of LKM positive hepatitis, particularly in terms of drugs as possible trigger factors.
Adult↗
Cost containment: coadministration of diltiazem with cyclosporine after heart transplantation.
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)
Cost Control↗
Initial steroid-free versus steroid-based maintenance therapy and steroid withdrawal after heart transplantation: two views of the steroid question.
To determine any benefit of maintenance steroids in a cyclosporine and azathioprine immunosuppressive regimen, 112 heart transplant recipients were prospectively randomized to receive cyclosporine, azathioprine, and prednisolone (n = 59) or cyclosporine and azathioprine (n = 53). Of the 53 double-therapy patients, 47% were converted to maintenance steroids for resistant rejection or renal dysfunction. In a comparison of true double-therapy (n = 28) versus true triple-therapy (n = 59) groups, actuarial survival and systolic function did not differ. Linearized rejection during the first 3 months was lower with triple therapy than with double therapy (1.5 +/- 0.18 vs 2.3 +/- 0.23 episodes/100 patient-days; p less than 0.01) as were requirements for cytolytic therapy for rejection with hemodynamic compromise. Patients receiving triple therapy had significantly higher serum cholesterol levels and antihypertensive agent requirements at all annual time points up to 5 years. The rate of steroid-related morbidity (diabetes, bone complications, cataracts, and obesity) was low in both groups and did not differ significantly. Of the 204 patients receiving triple therapy at this unit, 45 underwent steroid withdrawal. The initial success rate was 69%, and an additional 14% of those who initially failed succeeded on the second attempt. Any rejection after steroid cessation tended to occur within 6 weeks. There were, however, no substantial short-term benefits in body weight or lipid or blood pressure control. In patients in whom infection or growth retardation was an indication for steroid withdrawal, these generally improved after cessation. Until predictive markers for the likely success of steroid withdrawal are identified, the case for steroid withdrawal, as opposed to steroid minimization, does not seem compelling.
Adult↗
Five-year follow-up of a randomized double-drug versus triple-drug therapy immunosuppressive trial after heart transplantation.
To determine the role of maintenance steroids in a cyclosporine and azathioprine immunosuppressive regimen, 112 heart transplant recipients were prospectively randomized to group I (n = 59; cyclosporine, azathioprine, and prednisolone) or group II (n = 53; cyclosporine and azathioprine). All patients received 7 days of induction with antithymocyte globulin. Patients receiving double-drug therapy who required four treatments for rejection were converted to maintenance steroids. This was necessary in 47% of the patients. Actuarial survival at 5 years was 82% in group I and 85% in group II. Linearized rejection in the first 3 months was lower with triple-drug therapy than with double-drug therapy (1.5 +/- 0.18 versus 2.3 +/- 0.23 episodes/100 patient days, p less than 0.01) but did not differ beyond 3 months. No significant differences were noted in 3-year left ventricular ejection fraction (0.56 +/- 0.09 versus 0.58 +/- 0.12 units), serum creatinine level (0.14 +/- 0.04 versus 0.14 +/- 0.03 mmol/L), or number with coronary artery disease (10 versus 13), diabetes, or bone complications. Patients receiving triple-drug therapy, however, had higher serum cholesterol level at 3 years (6.2 +/- 0.9 versus 5.4 +/- 1.2 mmol/L; p = 0.022) and required more antihypertensive agents (1.3 +/- 0.8 versus 0.8 +/- 0.6; p = 0.016). Similar trends emerged when patients receiving true double-drug therapy were compared with those patients who were "converted." Therapy with double versus triple immunosuppressive therapy results in similar 5-year survival and systolic function, using this protocol of converting recurrent rejectors on double-drug therapy to maintenance steroids.(ABSTRACT TRUNCATED AT 250 WORDS)
Actuarial Analysis↗
Role of routine endomyocardial biopsy to monitor late rejection after heart transplantation.
Endomycardial biopsy remains the standard used to monitor rejection after heart transplantation. There is, however, no consensus as to how often surveillance endomyocardial biopsy should be carried out after heart transplantation. We have analyzed 131 patients undergoing orthotopic heart transplantation during the first 4 years of the transplant program at St. Vincent's Hospital. The majority of endomyocardial biopsies that showed acute rejection occurred in the first 3 months after transplantation; after 9 months only 2.5% of endomyocardial biopsies performed showed rejection. Of those patients with rejection, 47% had symptoms. Seven patients experienced late rejection and all made a good recovery with normal cardiac function. We conclude that the incidence of acute rejection decreases significantly more than 3 months after-transplantation; after 9 months only 2.5% of endomyocardial biopsies will show rejection. Of these, 47% will be associated with symptoms. On the basis of experience, we believe that in our own unit, endomyocardial biopsy more than 9 months after transplantation seems unwarranted unless clinically indicated.
Adult↗
Heart transplantation in females.
To confirm reports of a higher rate of rejection in female recipients of cardiac allografts and to determine whether infection rates and actuarial survival differ from that in males, we reviewed the results of 150 consecutive heart transplant procedures. Of these, 27 were in females and 123 were in males. Three different regimens were used over a 5-year period: group 1 (n = 37), cyclosporine and prednisolone; group 2 (n = 61), cyclosporine, azathioprine, and prednisolone; group 3 (n = 52), cyclosporine and azathioprine. All groups received a 7- to 10-day induction course with antithymocyte globulin. Female recipients had significantly more rejection episodes than male recipients to 3 months after transplantation (females 2.3 vs males 1.5 episodes/patient, p less than 0.01) and to 12 months (females 2.4 vs males 1.5 episodes/patient, p less than 0.02). These differences were largely caused by higher rates of rejection in females in both "double" therapy groups (groups 1 and 3). All surviving females in group 3 required the addition of maintenance steroids to control rejection. Gender mismatching of donors (male donor, female recipient) was identified as a factor associated with this requirement for conversion. Augmented treatment for rejection resulted in a higher rate of infection at 12 months in female recipients (females 1.5 vs males 0.7 episodes/patient, p less than 0.02), yet no female died of infection, and actuarial survival was comparable to that in male recipients. In view of the propensity of females to reject more frequently and earlier than males, triple therapy is currently the regimen of choice for female patients in the first 3 to 6 months after heart transplantation. Steroid withdrawal may be possible at a later time in those in whom this is indicated.
Actuarial Analysis↗
Atrial overdrive pacing for reversion of atrial flutter after heart transplantation.
Atrial overdrive pacing is an effective treatment to terminate classic (type 1) atrial flutter. After heart transplantation, the appearance of atrial flutter may be an indication of acute allograft rejection, and in patients who have this arrhythmia we routinely perform endomyocardial biopsy. In this study we examined the efficacy of atrial overdrive pacing performed at the time of endomyocardial biopsy in the termination of atrial flutter. Endomyocardial biopsy was performed with a Caves-Scholten bioptome via a right internal jugular venous sheath. After completion of the biopsy, a J-shaped 5F bipolar pacing lead was inserted via the sheath and positioned with the lead tip directed medially against the interatrial septum or right atrial appendage. Atrial pacing was performed with stimulation rates up to 450 beats/min at 20 mA for 15 seconds. Since July 1989, 16 episodes of atrial flutter have occurred in nine patients. Twelve episodes (75%) were associated with acute rejection, which was moderate or severe in nine cases. Atrial overdrive pacing was successful in restoring sinus rhythm in 13 of 14 episodes during which it was attempted (success rate, 93%). The procedure was uncomplicated and produced minimal patient discomfort. In comparison, of eight episodes of atrial flutter (in six patients) that occurred before the routine use of atrial overdrive pacing, seven were associated with rejection. With treatment of rejection, two episodes reverted spontaneously, but on six occasions cardioversion with patients under general anesthesia was necessary to restore sinus rhythm. In conclusion, atrial flutter occurring after heart transplantation is usually associated with acute allograft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial Flutter↗
The effect of chronic amiodarone therapy before transplantation on early cardiac allograft function.
Because of its long half-life, there has been concern that chronic amiodarone therapy before heart transplantation may adversely affect early cardiac allograft function and delay patient recovery. We retrospectively analyzed the outcome of the last 50 patients undergoing heart transplantation at our institution (between September 1988 and September 1989). Nineteen patients had been taking amiodarone at the time of transplantation (mean daily dose, 247 +/- 31 mg; mean duration of treatment, 9.0 +/- 2.2 months). These patients did not differ from the remaining 31 patients with respect to age, sex, or cause of disease. Donor organ ischemic time was also similar in the two groups (158 +/- 11 vs 153 +/- 10 minutes, NS). Patients who had received amiodarone before transplantation had significantly lower heart rates at 1 and 4 weeks after transplantation. They required atrial pacing for a longer time after transplantation compared with the remaining patients (7.3 +/- 1.4 vs 3.4 +/- 0.8 days, p less than 0.02). There was, however, no detectable effect of prior amiodarone therapy either on early allograft inotropic function or on clinical outcome. The mean time to hospital discharge was similar in the two groups. We believe that acceptance for heart transplantation should not be regarded as a contraindication to amiodarone therapy.
Adolescent↗
Hyperlipidemia after heart transplantation.
Because hyperlipidemia may be a factor in the development of late graft atherosclerosis after heart transplantation, we have studied serum lipid levels in patients during the first year after transplantation. Serum cholesterol and triglyceride levels were measured in the preoperative period and at regular intervals up to 12 months after transplantation in 22 consecutive heart transplant recipients. Patients were divided into two groups: group 1 included 10 patients with underlying ischemic heart disease, and group 2 had 12 patients with underlying idiopathic dilated or valvular cardiomyopathy. Mean serum cholesterol concentrations in both groups increased substantially after operation and peaked at 3 months (respective rises of 35% and 30%). By 12 months after transplantation 50% of group 1 and 33% of group 2 manifested a significant degree of hypercholesterolemia (plasma cholesterol greater than 6.5 mmol/L, 250 mg/100 ml). Mean serum triglyceride concentrations increased in both groups during the latter part of the first year (respective increases of 44% and 13%). At 12 months only 10% of group 1 and 8% of group 2 manifested a significant degree of hypertriglyceridemia (plasma triglycerides greater than 3.0 mmol/L, 265 mg/100 ml). Over the first postoperative year there was a progressive increase in body weight, and this correlated highly with the increase in serum lipid levels (r = 0.90 for serum cholesterol and r = 0.84 for serum triglycerides). The role of conventional risk factors including hypercholesterolemia in the development of graft atherosclerosis remains uncertain, but until their role is defined, further strenuous efforts at weight control as a means of preventing or managing hyperlipidemia need to be explored.
Adult↗
Doing the right thing.
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Education, Continuing↗
Organ transplants. The role of the transplant co-ordinator.
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Allied Health Personnel↗
HLA mismatching and outcome in heart, heart-lung, and single lung transplantation.
BACKGROUND: To determine the influence of HLA mismatching on rejection after cardiothoracic organ transplantation, we analyzed results in 243 recipients. METHODS: There were 183 heart, 25 heart-lung, and 35 single lung recipients, all receiving triple-drug immunosuppression with anti-thymocyte globulin induction. Zero, one, and two mismatches occurred by chance at each locus in between 0% to 9%, 26% to 35%, and 47% to 70% of recipients, respectively. RESULTS: In heart recipients, compared with a two mismatch, a zero mismatch was associated with a lower linearized rejection rate in the first 6 months. A zero B locus mismatch was likewise associated with less rejection in month 1, and DR zero mismatch with reduced rejection in the first 3 months. Steroid withdrawal was more successful in those with zero mismatch at any locus. In heart-lung recipients linearized rejection was significantly lower in those with lesser degrees of A and DR locus mismatching, and after single-lung transplantation linearized rejection was significantly lower with lesser degrees of A and B locus mismatching from 3 to 6 months only. Actuarial survival did not differ for any organ with any degree of mismatch at any locus. CONCLUSIONS: HLA mismatching affects rejection, but the effect is limited to the early postoperative period for heart and heart-lung recipients. Lower grades of mismatch increase the likelihood of successful steroid withdrawal for heart recipients. The chance occurrence of no mismatch at any locus is rare, making prospective matching infeasible. HLA mismatching identifies patients at higher risk of rejection. The best use of this information may be to guide early immunosuppression, limiting prospective matching to retransplants or with presensitized recipients.
Graft Rejection↗
Outcome in peripartum cardiomyopathy after heart transplantation.
From 1983 to 1991, 27 women with peripartum cardiomyopathy were considered for heart transplantation. Of 27 patients, 11 (41%) improved with medical therapy, 10 (37%) underwent transplantation, and six (22%) died. Results in the 10 patients with peripartum cardiomyopathy who underwent transplantation were compared with results in 39 women who underwent transplantation for dilated cardiomyopathy (idiopathic, Adriamycin, valvular, or familial) to determine whether there were differences in survival, rejection, or infection rates. The two groups were, by chance, well matched for number of pregnancies, peak panel reactivity, and cross-match. Mean time from delivery to transplantation was 24 weeks (range 2 to 188 weeks), and this time did not correlate with rejection rates. The linearized rate of rejection from 0 to 3 months was 30% higher in the group with peripartum cardiomyopathy (3.4 +/- 0.7 vs 2.6 +/- 0.3 episodes/100 patient days; p = 0.05). The mean postoperative day to first rejection was day 26 for peripartum cardiomyopathy and day 28 for women with dilated cardiomyopathy. Rejection requiring cytolytic therapy occurred in 40% of women with peripartum cardiomyopathy and 21% of the comparison group (difference not significant). Linearized (treated) infection rates were 1.8 +/- 0.5 for the group with peripartum cardiomyopathy versus 1.5 +/- 0.2 episodes/100 patient days for others (p = 0.05). Actuarial survival was excellent in both groups with 88% and 86% 2-year survival rates, respectively. In conclusion, women who undergo transplantation for peripartum cardiomyopathy have a 30% higher rate of early rejection than do those who undergo transplantation for idiopathic cardiomyopathy and tend to have a greater need for cytolytic therapy. Infection rates are consequently higher.(ABSTRACT TRUNCATED AT 250 WORDS)
Actuarial Analysis↗
Outcome in paired recipients of single lung transplants from the same donor.
BACKGROUND AND METHODS: We compared outcome measures in twenty single lung transplant recipients: 10 patients received the first lung of a donor pair (group 1), and 10 patients received the second lung (group 2) to determine the feasibility of sequential use, respectively, of donor lungs from the same donor in the same institution. The paired recipients underwent transplantation in the same operating room by the same surgical team. Both groups were well matched for age, gender, pretransplantation symptom class and diagnosis. RESULTS: The ischemic time for group 1 versus group 2 was 164 +/- 53 minutes (mean +/- standard deviation) (range 103 to 250 minutes) versus 377 +/- 53 minutes (range 315 to 445 minutes), respectively, (p < 0.001), but the longer ischemic time for group 2 did not adversely affect time to extubation (10.5 +/- 5.1 hours versus 10.3 +/- 7.6 hours; p = Not significant), early gas exchange (partial pressure of arterial oxygen on a fractional concentration of oxygen in inspired gas of 0.60: 237 +/- 61 versus 267 +/- 88 mm Hg; p = Not significant), length of hospital stay (16 +/- 13 days versus 16 +/- 5 days; p = Not significant), or actuarial one-year survival (80 +/- 12% versus 90 +/- 12%; p = Not significant). However, acute lung rejection (expressed as events/100 days) was more common within the first 3 months in group 1 versus group 2 (2.68 +/- 0.57 versus 1.32 +/- 0.38, respectively; p < 0.01), as were infectious events (2.07 +/- 0.50 versus 0.99 +/- 0.33; p < 0.01). CONCLUSIONS: These data confirm the safety of using the second lung from a donor pair sequentially in the same institution. The longer cold ischemic time for the second lung does not impair demonstrably early graft function and may be associated with a lower perioperative morbidity from acute rejection and subsequent infection. One-year outcome appears favorable for both groups.
Adolescent↗
Pilot study of low-dose azathioprine in presensitized patients awaiting heart or lung transplantation.
In an effort to reduce the level of presensitization in patients on our heart and lung transplant waiting list, ten patients with random panel reactivity above 10% on monthly screening for durations of 2 to 59 months were given low-dose azathioprine (25 to 75 mg/day) for 1 to 22 months. All patients had positive T-cell panel reactivity (10% to 70%) against specific (n = 6), multi-specific (n = 1), or undefined (n = 3) HLA loci, and four additional patients had positive B-cell panel reactivity (5% to 40%). No effect of azathioprine on panel reactivity was seen in four of ten patients (40%), whereas a significant and sustained reduction in panel reactivity occurred in six patients (60%), all within 2 months of commencing azathioprine. All nonresponders had antibodies with class I (A locus) specificity, whereas all six responders had multi-specific or undefined antibody specificities. A formal trial of low-dose azathioprine in presensitized recipients is warranted.
Adult↗