Search PubMed⌕ Search

Biomedical subjects

S A Hunt

Publications and source records attributed to S A Hunt.

At least 19 recordsLinked to original sources

Severe tricuspid regurgitation after heart transplantation.

BACKGROUND: Tricuspid regurgitation (TR) is common after heart transplantation. However, the incidence of severe TR and the incidence of symptoms after echocardiographic diagnosis of severe TR have not been documented. The purpose of this study is to determine the incidence of severe TR and its clinical significance in the heart transplant population. METHODS: We reviewed echocardiograms (echo) of all heart transplant patients coming for regular echocardiographic follow-up between 1990 and 1995. We reviewed the charts of all patients who had echo diagnosis of severe TR. RESULTS: A total of 336 patients had echo follow-up during this time period. The number of months post-heart transplant to last echo was 54 +/- 50 (range, 1 to 265 months). Ninety patients had moderate TR and 23 patients had severe TR. Mean time from heart transplantation to diagnosis of severe TR was 43 +/- 38 months (range, 1 to 132). Using Cutler-Ederer analysis, at 5 years, 92.2% of surviving patients were free from severe TR. At 10 years, 85.8% of surviving patients were free from severe TR. Of the 23 patients with severe TR, 17 had charts available for review. The mean number of prior endomyocardial biopsies was 28 +/- 21 (range, 3 to 88). These patients were followed for 35 +/- 18 months after diagnosis. During this period, they developed significant heart failure and peripheral edema. Six patients eventually underwent tricuspid valve replacement. CONCLUSIONS: Moderate to severe TR commonly occurs following heart transplantation. Severe TR is associated with significant morbidity.

Adult↗

Mild hyperhomocysteinemia is not associated with cardiac allograft coronary disease.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for coronary disease and elevated plasma homocysteine levels have been documented in heart transplant recipients. The aim of this study was to test the hypothesis that homocysteine levels are associated with presence or absence of transplant coronary artery disease. METHODS: Forty-three non-smoking adults were recruited, all of whom had received a heart transplant between 2 and 7 yr previously. All 43 had blood drawn for fasting homocysteine level on the day of presentation. All patients had undergone diagnostic coronary angiography within the past 6 months. RESULTS: For all patients, the average fasting plasma homocysteine level was 17.0+/-SD 6.6 micromol/L with a range from 6.0 to 36.9 micromol/L. Twenty-six patients (60%) had fasting plasma homocysteine levels above 15.0 micromol/L. On the basis of arteriography, patients were categorized as those with angiographically normal (n=22) or abnormal (n=21) coronary arteries. There was no difference in the mean plasma homocysteine level comparing patients with angiographically normal (17.2+/-SD 7.0 micromol/L) to those with abnormal (16.8+/-SD 6.2 micromol/L) coronary arteries. Plasma homocysteine levels increased with increasing plasma creatinine levels (r=0.63, p<0.0001) and with decreasing vitamin B6 levels (r=-0.56, p<0.0001). CONCLUSIONS: Mild hyperhomocysteinemia is a consistent finding among heart transplant recipients. This finding was not associated with transplant coronary artery disease in our patients. The combination of renal dysfunction and vitamin B6 deficiency may explain the unusual prevalence of hyperhomocysteinemia in heart transplant recipients.

Adult↗

New technique for treatment of unstable distal femur fractures by locked double-plating: case report and biomechanical evaluation.

BACKGROUND: A comminuted, intra-articular distal femur fracture was surgically treated by the authors with a locked, double-plating technique because fixation stability could not be initially achieved by using a standard double-plating technique. The purpose of this study was to determine biomechanically whether a locked double-plate construct would enhance fixation stability compared with a nonlocked double-plate construct. METHODS: Six matched pairs of mildly osteopenic femurs were selected and all had a reproducible intra-articular fracture pattern created. Each pair underwent fixation with either a double-plating construct or a locked, double-plating construct that was randomly assigned. The instrumented femurs were then mechanically tested in several loading modes to determine fixation stability. After initial testing, specimens were cyclically loaded and retested for stability. RESULTS: The locked, double-plating construct provided significantly greater fixation stability than the standard double-plating construct in precycling and postcycling biomechanical testing. CONCLUSION: The technique described is particularly applicable for severely comminuted fractures of the distal femur and fractures in osteopenic bone with poor screw purchase. It offers a simple alternative for enhancing fixation stability, which avoids the potential complications of methylmethacrylate-enhanced screw fixation.

Biomechanical Phenomena↗

Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebo-controlled study.

BACKGROUND: Coronary artery disease occurs in an accelerated fashion in the donor heart after heart transplantation (TxCAD), but the cause is poorly understood. The risk of developing TxCAD is increased by cytomegalovirus (CMV) infection and decreased by use of calcium blockers. Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness, and we now propose to determine whether this therapy also prevents TxCAD. METHODS AND RESULTS: One hundred forty-nine consecutive patients (131 men and 18 women aged 48+/-13 years) were randomized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation. Immunosuppression consisted of muromonab-CD3 (OKT-3) prophylaxis and maintenance with cyclosporine, prednisone, and azathioprine. Mean follow-up time was 4.7+/-1.3 years. In a post hoc analysis of this trial designed to assess efficacy of ganciclovir for prevention of CMV disease, we compared the actuarial incidence of TxCAD, defined by annual angiography as the presence of any stenosis. Because calcium blockers have been shown to prevent TxCAD, we analyzed the results by stratifying patients according to use of calcium blockers. TxCAD could not be evaluated in 28 patients because of early death or limited follow-up. Among the evaluable patients, actuarial incidence of TxCAD at follow-up (mean, 4.7 years) in ganciclovir-treated patients (n=62) compared with placebo (n=59) was 43+/-8% versus 60+/-10% (P<0.1). By Cox multivariate analysis, independent predictors of TxCAD were donor age >40 years (relative risk, 2.7; CI, 1.3 to 5.5; P<0.01) and no ganciclovir (relative risk, 2.1; CI, 1.1 to 5.3; P=0.04). Stratification on the basis of calcium blocker use revealed differences in TxCAD incidence when ganciclovir and placebo were compared: no calcium blockers (n=53), 32+/-11% (n=28) for ganciclovir versus 62+/-16% (n=25) for placebo (P<0.03); calcium blockers (n=68), 50+/-14% (n=33) for ganciclovir versus 45+/-12% (n=35) for placebo (P=NS). CONCLUSIONS: TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.

Actuarial Analysis↗

Thirty years of cardiac transplantation at Stanford university.

BACKGROUND: The experience with 30 years of cardiac transplantation at Stanford University Medical Center was reviewed. A total of 954 transplants were performed in 885 patients. Patients were divided into 3 groups based on immunosuppression received: group I, no cyclosporine (INN: ciclosporin) (n = 201) (January 1968-November 1980); group II, cyclosporine (n = 248) (December 1980-June 1987); and group III, cyclosporine + OKT3 (n = 436) (July 1987-March 1998). RESULTS: The 1-, 5-, and 10-year actuarial survivals were 68%, 41%, and 24% (group I); 80%, 57%, and 37% (group II); and 85%, 68%, and 46% (group III) (I vs II, P <.01; I vs III, P <.005; and II vs III, P <.005). The 1-, 5-, and 10-year actuarial death rates from rejection were 8%, 12%, and 14% (group I); 5%, 7%, and 7% (group II); and 2%, 5%, and 5% (group III) (I vs II, P = not significant; I vs III, P <.005; and II vs III, P <.005). The 1-, 5-, and 10-year actuarial death rates from infection were 25%, 43%, and 50% (group I); 8%, 17%, and 29% (group II); and 6%, 11%, and 16% (group III) (I vs II, P <.005; I vs III, P <.005; and II vs III, P <.05). The 1-, 5-, and 10-year actuarial death rates from graft coronary artery disease were 0%, 5%, and 13% (group I); 0%, 12%, and 19% (group II); and 1%, 6%, and 9% (group III) (I vs II, P <.01; I vs III, P <.005; and II vs III, P = not significant). There have been 69 retransplants in 67 patients with 1-, 5-, and 10-year actuarial survivals of 49%, 27%, and 15%, respectively. CONCLUSIONS: The evolution of 3 decades of experience with cardiac transplantation has resulted in improved overall survival. The incidence of rejection and of death from infection and graft coronary artery disease have decreased over time, primarily as a result of improvements in immunosuppression and in the prevention and treatment of infection. Continued advances in perioperative management and the development of more specific, less toxic immunosuppressive agents could further refine this initial experience and improve the survival and quality of life of patients after cardiac transplantation.

Academic Medical Centers↗

Current status of cardiac transplantation.

Cardiac transplantation, first introduced 30 years ago, has become a widely used and increasingly important procedure for treatment of truly end-stage heart disease. Current use is limited strictly by donor supply, making selection of appropriate recipients an important ethical and societal issue. Survival rates after transplantation rose in the 1980s with the use of cyclosporine and have remained relatively consistent since then, although recipients older than 65 years or younger than 1 year have lower survival rates than recipients of other ages. Although immunosuppressive drugs have helped establish cardiac transplantation as a successful procedure, risks of opportunistic infection and rejection, as well as coronary arteriopathy, have led to development of new immunosuppressive agents currently under study. Future alternatives to the current technology of cardiac allotransplantation may include xenotransplantation and/or nonbiological replacement of the heart with mechanical devices.

Forecasting↗

Long-term results of total lymphoid irradiation in the treatment of cardiac allograft rejection.

PURPOSE: To evaluate the short and long-term effects of total lymphoid irradiation (TLI) in the treatment of cardiac transplant rejection. METHODS AND MATERIALS: Between 1986 and 1995, 48 courses of TLI were delivered to 47 cardiac transplant patients. In 37 patients, TLI was administered for intractable allograft rejection despite conventional therapy while 10 patients received TLI prophylactically. The prescribed radiation dose was 8 Gy in 0.8 Gy fractions twice weekly to mantle and inverted-Y plus spleen fields. Postirradiation follow-up ranged from 6 months to 9.1 years, with a mean of 3.1 years. RESULTS: The actual mean dose was 7.3 Gy delivered over a mean of 39 days. Fifty-six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, rejection rates dropped from 0.46 to 0.14 and to 0.06 episodes/patient/month before, during, and after TLI (p < 0.0001). Rejection rates continued to drop throughout follow-up. Prednisone requirements decreased from 0.41 mg/kg before treatment to 0.21 mg/kg afterward (p < 0.0001). The ratio of helper to cytotoxic-suppressor T-cells decreased during TLI from 1.33 to 0.89, and remained low at 0.44, 2-4 months after treatment. Infection rates were not increased and two patients developed malignancy. Rejection rates were high during prophylactic treatment and this protocol was abandoned. Three-year actuarial survival after irradiation was 60% for patients with intractable rejection and 70% for the prophylactic cohort. CONCLUSION: TLI is an effective treatment for control of intractable cardiac rejection. Episodes of rejection and steroid dosage requirements are decreased for up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. Long-term complications of TLI are not appreciably different than conventional immunosuppression.

Adolescent↗

Relation of donor age and preexisting coronary artery disease on angiography and intracoronary ultrasound to later development of accelerated allograft coronary artery disease.

OBJECTIVES: This study assessed the influence of donor age and preexisting donor coronary disease on the later development of allograft coronary artery disease, ischemic events and overall survival. BACKGROUND: The increasing demand for heart donors has led to a tendency to liberalize age criteria for donor acceptability. METHODS: A total of 233 consecutive heart transplant recipients who had baseline, early postoperative and follow-up coronary angiograms, as well as a subset of 47 patients with baseline intracoronary ultrasound imaging recordings, were analyzed (mean 3.8 years of follow-up). Patients were subclassified according to the presence of donor coronary artery disease on the baseline angiogram and stratified at age 40 years. RESULTS: patients without evidence of preexisting coronary artery disease on a baseline angiogram (n = 219) were significantly less likely to develop new disease than the 14 patients with preexisting coronary artery disease (p = 0.002). Although older donors exhibited earlier coronary artery disease than younger donors at 3 years of follow-up, there was no difference by 5 years (p = 0.25). There was no difference in survival or probability of developing ischemic events between the groups. Baseline ultrasound imaging revealed substantial disease in 7 of 9 older donated hearts, and in only 7 of 38 younger donated hearts (p = 0.002). Preexisting coronary artery disease, nonuse of calcium channel blocking agents, older donor age, posttransplantation cytomegalovirus infection, elevated very low density lipoprotein levels and previous ischemic heart disease in the recipient were significant predictors of allograft coronary artery disease. CONCLUSIONS: Heart donors with angiographic evidence of preexisting coronary artery disease and older donors are more likely to develop new allograft coronary artery disease by 3 years. However, there is no difference in survival or freedom from ischemic events between younger and older donors at a mean follow-up of 3.8 years.

Adolescent↗

Methotrexate or total lymphoid radiation for treatment of persistent or recurrent allograft cellular rejection: a comparative study.

BACKGROUND: Methotrexate and total lymphoid irradiation (TLI) have been used successfully for treatment of recurrent and persistent rejection in orthotopic heart transplant recipients; however, there has been no comparison of these two modalities. METHODS: We retrospectively compared the efficacy of methotrexate (n = 29) versus TLI (n = 28) in heart transplant recipients with recurrent or persistent rejection. All patients received induction therapy (rabbit anti-thymocyte globulin or OKT3) and standard triple immunosuppressive therapy. Methotrexate (7.5 mg to 22.5 mg per wk) or TLI (80 cGy x 10 fractions) was used for the treatment of recurrent or persistent rejection on the basis of clinical indications. Average biopsy scores (International Society of Heart and Lung Transplantation biopsy score/total number of biopsies performed) calculated over 3-month periods, daily maintenance prednisone dose before and after methotrexate or TLI treatment, and actuarial survival and freedom from angiographic coronary artery disease and infection were compared. To control for the general decrease in prednisone with increased time from transplantation, a control group matched for time from transplantation was selected. RESULTS: Recipient sex and age at transplant, donor age, and donor ischemic time were similar in both groups. Days after transplantation to start of therapy was longer in patients receiving methotrexate; however, this did not reach statistical significance. Patients receiving TLI had received more cumulative corticosteroids and OKT3 before the start of TLI therapy (p < 0.001). There were no differences in actuarial freedom from infection or coronary artery disease between the two groups and between the treatment groups and the control group. Actuarial survival was reduced in patients receiving TLI 3 years after transplantation (p < 0.05). Maintenance prednisone doses from 3 months before until 9 months after therapy (mg/kg) were not different between patients receiving TLI and methotrexate and were significantly greater than the prednisone doses in the control group. Four months after treatment initiation, the prednisone dose was significantly reduced in both treatment groups compared with the pretherapy dose (methotrexate 0.28 +/- 0.16 to 0.22 +/- 0.13, p = 0.05; TLI 0.36 +/- 0.16 to 0.22 +/- .07, p < 0.001). The average biopsy score was significantly reduced by both methotrexate and TLI therapy (methotrexate 1.8 +/- 0.7 to 0.83 +/- 0.9, p = 0.0001; TLI 2.1 +/- 0.8 to 1.0 +/- 0.9, p = 0.0001). CONCLUSION: Methotrexate and TLI are both effective for the treatment of recurrent or persistent rejection after heart transplantation, reducing average biopsy scores and daily maintenance prednisone doses. There was a reduction in actuarial survival rates in patients treated with TLI, possibly reflecting the greater rejection therapy received before TLI initiation. Because both agents are effective, the choice of methotrexate or TLI may be based on clinical indications, as well as other issues, such as cost, compliance, and availability.

Actuarial Analysis↗

Heart transplantation in patients over 54 years of age. Mortality, morbidity and quality of life.

AIMS: As a consequence of recent advances in heart transplantation, upper age limits for the procedure have been liberalized in many centres. It was the purpose of this study to compare post-transplant mortality, morbidity and quality of life in a consecutive series of 72 patients > 54 years (mean age, 57.6 +/- 2.7 years) with a control group of 72 adult patients < or = 54 years (mean age, 42.4 +/- 9.5 years) transplanted at one centre between 1985 and 1991. METHODS AND RESULTS: Patients were followed for 41 +/- 27 months post-transplant. Actuarial 1-, 5- and 7-year survival rates were 78 +/- 5%, vs 81 +/- 5%, 52 +/- 7% vs 66 +/- 6% and 46 +/- 8% vs 63 +/- 6% in patients > 54 years and < or = 54 years, respectively (P = ns). Causes of death were not significantly different between the groups. Patients > 54 years experienced significantly fewer rejection episodes after the 6th month post-transplant (0.5 +/- 0.9 vs 0.9 +/- 1.0, P < 0.04), and incidence and treatment of rejection episodes as well as incidence of infection was comparable between the groups. Non-lymphoid malignancies, mainly skin cancer, occurred more often in the older age group (27% vs 13%, P < 0.05). Quality of life, as assessed by the Nottingham Health Profile, was better in 5/6 dimensions of social functioning in older patients and the difference reached statistical significance for the dimensions of emotional reactions (P = 0.005) and sleep (P = 0.0005). CONCLUSION: In conclusion, carefully selected patients > 54 years can undergo heart transplantation with mortality and morbidity comparable to younger patients. Quality of life post-transplant seems even to be slightly better in the older age group.

Actuarial Analysis↗

Early Doppler echocardiographic dysfunction is associated with an increased mortality after orthotopic cardiac transplantation.

BACKGROUND: Doppler echocardiographic (DE) diastolic dysfunction has been correlated with rejection after orthotopic cardiac transplantation (Tx). However, the relationship of early diastolic dysfunction to late outcome is unknown. The purpose of this study was to assess the correlation between early DE diastolic dysfunction and outcome after heart Tx. METHODS AND RESULTS: Of 133 patients undergoing heart Tx between October 1990 and April 1994, 83 were identified with > or = 4 routine DE performed during the first 6 months. Assessment of diastolic function included measurement of isovolumic relaxation time (IVRT), pressure half-time (PHT), and peak early mitral inflow velocity (M1). Diastolic dysfunction was defined as a decrease of 15% from baseline (IVRT and PHT) or an increase of 20% (M1). A mean dysfunction score (MDS) was calculated for each patient (number of episodes of dysfunction by Doppler total number of echocardiograms performed). The population diastole MDS was determined and two groups established (group 1, MDS < mean; group 2, MDS > mean). Actuarial survival, rejection, and transplant coronary artery disease (TxCAD) were compared between groups. Actuarial survival was significantly reduced in patients with greater early diastolic dysfunction (P < .05). There were 17 deaths overall: 5 in group 1 (mean, 786 days) and 12 in group 2 (mean, 384 days). There were no significant differences in treated rejection episodes, actuarial freedom from rejection or TxCAD, immunosuppression, sex, donor age, donor ischemic time, or cytomegalovirus between the two groups. CONCLUSIONS: Diastolic dysfunction within 6 months of transplant was associated with an increased late mortality.

Adult↗

Are heart-lung transplant recipients protected from developing transplant coronary artery disease? A case-matched intracoronary ultrasound study.

BACKGROUND: Accelerated coronary artery disease is a major cause of mortality in heart transplant recipients; however, it does not appear to play a major role in the clinical outcome of heart-lung transplant recipients. The purpose of this study was to determine whether the incidence and severity of transplant coronary artery disease as detected by intracoronary ultrasound in heart-lung transplant recipients are less than those encountered in heart transplant recipients. METHODS AND RESULTS: We studied the left anterior descending coronary artery with the use of intracoronary ultrasound imaging in 22 heart-lung transplant recipients at the time of their routine annual coronary angiogram. Twenty-two heart transplant recipients were case matched for number of years after transplant at ultrasound study, recipient age, donor age, and diagnosis of nonischemic cardiomyopathy. Mean intimal area, intimal index, Stanford class, and incidence of at least moderate disease (Stanford class > or = 3) were measured and calculated in each group and then compared between the two groups. Mean intimal area (1.6 +/- 2.5 versus 3.8 +/- 2.8 mm2), mean intimal index (0.07 +/- 0.10 versus 0.22 +/- 0.14), mean Stanford class (1.7 +/- 1.0 versus 2.7 +/- 1.2), and incidence of Stanford class > or = 3 (14% versus 45%) were significantly lower in the heart-lung transplant recipient group. CONCLUSIONS: The incidence and severity of transplant coronary artery disease are much less in patients receiving heart-lung transplants than in those receiving heart transplants alone.

Adult↗