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D D Stapleton

Publications and source records attributed to D D Stapleton.

At least 19 recordsLinked to original sources
PubMed2000

Rhabdomyolysis and acute renal failure in a cardiac transplant recipient due to multiple drug interactions.

BACKGROUND: The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors lovastatin and simvastatin have been associated with rhabdomyolysis in cardiac transplant recipients. Herein, we report a case of a 52-year-old male recipient of a cardiac transplant who developed rhabdomyolysis and acute renal failure caused by simvastatin precipitated by multiple drug interactions. METHODS: The patient had a history of cardiac transplantation (5 years before) and presented with a 2-day history of dark urine preceded by 2 weeks of diffuse myalgias. He had been maintained on cyclosporine throughout the entire post-transplant period. Simvastatin was added and pravastatin was discontinued 2 months before admission. Two weeks before the onset of muscle symptoms, digoxin and verapamil were started for new-onset atrial fibrillation. Creatinine phosphokinase levels peaked at 950,000 IU with serum creatinine of 3.3 mg/dL (baseline, 1.8 mg/dL). RESULTS: Review of the medication history indicates a temporal association between the addition of 3 drugs (simvastatin, verapamil, and digoxin) to the medication regimen already containing cyclosporine and the episode of rhabdomyolysis. All of these drugs are cytochrome P450 3A4 and/or P-glycoprotein substrates that are known from previous pharmacokinetic studies to individually produce substantial increases in levels of simvastatin. CONCLUSION: We believe this case illustrates that avoiding the use of drugs that are cytochrome P450 3A4 and/or P-glycoprotein substrates reduces the risk of rhabdomyolysis caused by 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors.

Acute Kidney Injury↗
PubMed1998

Effects of caregiver specialty on cost and clinical outcomes following hospitalization for heart failure.

In 614 consecutive hospitalizations with the primary discharge diagnosis of diagnosis-related group (DRG) 127 (heart failure and shock), we sought to assess the effect of caregiver specialty (generalist, n = 217; cardiologist, n = 397) on hospital costs, length of stay, and in-hospital mortality. Patients treated by cardiologists were younger (68 vs 71 years) and less likely to have hypertension (52% vs 61%), but were more likely to be men (61% vs 44%), require an intensive care stay (13% vs 5%), have coronary artery disease (49% vs 23%), have a left ventricular ejection fraction <40% (74% vs 49%), and have lower systolic (132 vs 146 mm Hg) and diastolic (76 vs 81 mm Hg) blood pressures on admission. Predictors of acute disease severity were similarly distributed between the 2 groups. No difference was found between patients treated by cardiologists versus those treated by generalists with respect to crude or adjusted hospital cost, length of stay, and in-hospital mortality. However, in subsets of patients who required intensive care during hospitalization (n = 64), as well as those who did not (n = 550), care by cardiologists was associated with a lower adjusted hospital cost. Any potential cost savings that could have accrued from care by cardiologists was, however, negated by the higher proportion of patients treated by cardiologists who required intensive care during hospitalization. We conclude that when differences in clinical variables are adjusted, care by cardiologists versus generalists is associated with similar or lower hospital cost for patients with DRG 127. Our findings challenge the notion that in-patient care provided by specialists is more expensive than that provided by generalists.

Adult↗
PubMed1998

Mitral inflow and pulmonary venous Doppler measurements do not predict pulmonary capillary wedge pressure in heart transplant recipients.

BACKGROUND: Noninvasive estimation of pulmonary capillary wedge pressure (PCWP) with Doppler-derived mitral inflow pattern has been shown to correlate well with invasively measured PCWP; however, it has not yet been determined whether Doppler-derived mitral inflow pattern can be used to estimate PCWP accurately in heart transplant recipients. METHODS: To determine if mitral and pulmonary venous inflow data can be applied to calculate PCWP in heart transplant recipients, some-day echocardiograms and right heart catheterizations were reviewed and 83 echocardiograms with adequate mitral inflow patterns in 53 patients were studied. Twenty-eight studies that also had adequate pulmonary venous inflow patterns were selected for offline analysis. RESULTS: Using a previously published formula [PCWP = 17 + (5.3 x E/A) - (0.11 x IVRT)], where E/A is the ratio of early to late mitral inflow velocities and IVRT is the isovolumic relaxation time, we derived a calculated PCWP, the results of which compared poorly with the measured PCWP (r = 0.33; p = 0.002). Linear regression analysis of measured PCWP versus mitral inflow Doppler flow velocity parameters also revealed poor to modest correlation. Adding parameters derived from the pulmonary venous inflow patterns failed to improve this correlation. CONCLUSION: Doppler-derived estimation of PCWP with mitral and pulmonary venous inflow patterns cannot be used to reliably predict PCWP in heart transplant recipients.

Adolescent↗
PubMed1997

Home inotropic therapy in advanced heart failure: cost analysis and clinical outcomes.

STUDY OBJECTIVES: This study was conducted to assess cost savings and clinical outcomes associated with the use of home i.v. inotropic therapy in patients with advanced (New York Heart Association [NYHA] class IV) heart failure. DESIGN: Retrospective analysis. SETTING: Tertiary care referral center. PATIENTS AND INTERVENTIONS: Twenty-four patients (13 men, 11 women; age, 61+/-12 years) with left ventricular ejection fraction <30% and heart failure refractory to oral agents required home i.v. inotropic therapy for at least 4 consecutive weeks between May 1994 and April 1996. Inotropic agents used included dobutamine (n=20; dose, 5.0+/-2.2 microg/kg/min) or milrinone (n=7; dose, 0.53+/-0.05 microg/kg/min). MEASUREMENTS AND RESULTS: Cost of care and clinical outcomes (hospital admissions, length of hospital stay, NYHA functional class) were compared during the period of inotropic therapy (study period) and the immediate preceding period of equal duration (control period). In comparison to the control period, the study period (3.9+/-2.7 months) was associated with a 16% reduction in cost, amounting to a calculated savings of $5,700 per patient or $1,465 per patient per month. Concomitantly, a decrease in the number of hospital admissions from 2.7+/-2.6 to 1.3+/-1.3 (p=0.056) and length of hospital stay from 20.9+/-12.7 to 5.5+/-5.4 days (p=0.0004) was observed with improvement in NYHA functional class from 4.0+/-0.0 to 2.7+/-0.9 (p<0.0001). Eight patients (38%) died after 2.8+/-1.7 months of home i.v. inotropic therapy. CONCLUSIONS: Home i.v. inotropic therapy reduces hospital admissions, length of stay, and cost of care and improves functional class in patients with advanced (NYHA class IV) heart failure.

Cardiotonic Agents↗
PubMed1997

Usefulness of peak oxygen consumption in predicting outcome of heart failure in women versus men.

This investigation finds that percent of predicted maximum oxygen consumption, an age- and gender-adjusted measurement of exercise, capacity, describes the degree of functional impairment in women more accurately than peak oxygen consumption. This evidence must be considered when cardiopulmonary metabolic parameters are used for prognostic stratification of women with heart failure.

Cardiomyopathy, Dilated↗
PubMed1997

Safety and clinical utility of long-term intravenous milrinone in advanced heart failure.

Few data are available on the long-term safety or clinical utility of the inodilator agent milrinone. We designed a prospective, nonrandomized, observational trial in a cohort of 71 patients who had demonstrated dependence on inotropic therapy, had been clinically stable on an inotropic regimen (milrinone, dobutamine, or both) for > or = 72 hours, and had been given intravenous milrinone for > 72 hours. Group I (n = 22) patients required treatment with both milrinone and dobutamine to achieve stability; group II (n = 49) patients attained stability initially with either milrinone (subgroup IIA) or dobutamine (subgroup IIB), but later required adjunctive therapy with the other inotropic agent for continued hemodynamic support. Of the 71 patients, 38% required mechanical intervention to achieve hemodynamic stability, and 68% were successfully bridged to heart transplantation. Patients were maintained on milrinone therapy for as long as 8 weeks and demonstrated a low incidence of adverse cardiac (7%) or noncardiac (4%) events. Subgroup IIA (28%) had significantly less need than subgroup IIB (52%) for mechanical intervention using an intraaortic balloon pump (p = 0.05), although mortality rates while awaiting transplantation were statistically similar in subgroups IIA (28%) and IIB (35%). Significant improvements from baseline values were noted at the time of transplantation for all aspects of systemic hemodynamics, indicating sustained long-term hemodynamic effects. Long-term intravenous milrinone therapy is safe and well tolerated, and it provides hemodynamic and metabolic support as a pharmacologic bridge to transplantation. The findings also suggest that milrinone as primary inodilator therapy may be associated with less need for mechanical ventricular support.

Adult↗
PubMed1997

Allograft aortopathy: an in vivo study of donor aorta involvement in cardiac allograft vasculopathy.

Limited histopathologic studies of failed cardiac allografts have demonstrated that cardiac allograft vasculopathy extends into the donor aorta; however, no study has examined the development of allograft aortic intimal proliferation in vivo in conjunction with coronary intimal hyperplasia. By using simultaneous intracoronary and intraaortic ultrasound, we studied 20 consecutive heart transplant recipients at 2.5 +/- 2.1 years after transplantation. The degree of coronary intimal thickening was strongly correlated with the development of intraaortic intimal hyperplasia (r = 0.90; p < 0.0001). Multivariate predictors of aortic intimal thickening included years after transplant (r = 0.47; p = 0.03), serum cholesterol level (r = 0.65, p = 0.003), and serum triglyceride level (r = 0.51; p = 0.03). Allograft aortopathy occurs in a similar manner to allograft coronary disease, thus providing support for the notion that an immunologic stimulus operating across the allograft vascular bed may be responsible for the development of cardiac allograft vasculopathy. Furthermore, this investigation provides insight into the putative role of hyperlipidemia in allograft vascular disease.

Aorta↗
PubMed1997

Cyclosporine-induced hypertension in cardiac transplantation.

Cyclosporine-induced hypertension occurs in more than 90% of patients following cardiac transplantation. This article underlines the clinical characteristics as well as the mechanisms that can be associated with the development of cyclosporine-induced hypertension. In addition, the clinical trials up to date for the treatment of hypertension following cardiac transplantation are discussed. However, in view of the possible long-term sequelae associated with cyclosporine-induced hypertension, further studies to evaluate the long-term efficacy and safety of antihypertensive agents and finally the long-term effects of hypertension on the cardiac allograft are needed.

Antihypertensive Agents↗
PubMed1997

Heterogeneity of cardiac allograft vasculopathy: clinical insights from coronary angioscopy.

OBJECTIVES: With this study, we sought to examine the heterogeneity of cardiac allograft vasculopathy in vivo using coronary angioscopy as an adjunct to intravascular ultrasound, and we evaluated the clinical relations of immunologic and nonimmunologic risk factors with the different forms of cardiac allograft vasculopathy detected angioscopically. BACKGROUND: Intravascular ultrasound detects vascular intimal proliferation accurately but is limited in its ability to delineate morphologic characteristics. Coronary angioscopy can evaluate intimal surface morphology by direct visualization and can differentiate pathologically distinct forms of plaque topography on the basis of color and contour. METHODS: We studied 107 consecutive heart transplant recipients with intravascular ultrasound and angioscopy at the time of their annual angiogram, and we assessed the relation of nonimmunologic and immunologic risk factors to the development of cardiac allograft vasculopathy distinguished angioscopically into a pigmented (yellow) or nonpigmented (white) intimal thickening. We further evaluated the clinical differences in cardiac events among these two forms of angioscopically heterogeneous forms of cardiac allograft vasculopathy. RESULTS: Significant clinical predictors of nonpigmented intimal thickening were advanced donor age and lower mean cyclosporine levels, whereas hyperlipidemia, cumulative prednisone dose and time since transplantation correlated with pigmented intimal hyperplasia. In addition, comparisons between the two angioscopic groups revealed increased intimal thickening, serum cholesterol, low density lipoprotein cholesterol, acute allograft rejection and time since transplantation in the group with pigmented intimal thickening (p < 0.05). With regard to cardiac events, nonpigmented plaque was more frequently found in the sudden death group (53% vs. 20%, p = 0.05), whereas the nonsudden cardiac event group had a significantly higher prevalence of pigmented plaque (80% vs. 47%, p = 0.07). CONCLUSIONS: These findings indicate that cardiac allograft vasculopathy is a heterogeneous disease with varied morphologic expressions with different clinical implications. Furthermore, this investigation provides insight into the cohesive, yet diverse influences of various factors, particularly immunosuppression, in these forms of cardiac allograft vasculopathy.

Adult↗
PubMed1997

Implications for the vascular surgeon with prolonged (3 to 89 days) intraaortic balloon pump counterpulsation.

PURPOSE: The intraaortic balloon pump (IABP) is useful in the treatment of failing hearts. Although most experience with IABPs has been with acute short-term use, the safe duration of therapy and possible complications of long-term IABP use are uncertain. We evaluated the feasibility, management, and complications associated with long-term IABP therapy. METHODS: Fifty consecutive patients with 87 IABPs were evaluated retrospectively. All patients had IABP support for greater than 72 hours. Results and complications were evaluated. RESULTS: The mean duration of IABP support was 23.2 days. There were 21 IABP-related complications in 16 patients: (16 ischemic, three infections, two hemorrhage). The rate of complications was 0.13 per patient-week of support. Significant predictors of complications were total days of IABP support (p < 0.0001), use of multiple IABPs (p < 0.0001), and attempted but unsuccessful percutaneous insertions (p < 0.001). Complications led to 14 vascular procedures (five patch angioplasties, four bypass procedures, two major amputations, one fasciotomy, one groin exploration for hemorrhage, and one removal of an infected Dacron patch). Percutaneous removals had a 14% complication rate compared with none after operative removal (p = 0.02). Thirty-two patients survived (64%). Of the survivors, 27 underwent transplant. CONCLUSIONS: Prolonged IABP therapy is feasible and is associated with an acceptable rate of complications. Operative removal is superior to percutaneous removal. Percutaneous removal should be limited to short-term therapy. There is no need for mandatory removal or site rotation based solely on indwelling time.

Adult↗
PubMed1997

The prognostic impact of immunosuppression and cellular rejection on cardiac allograft vasculopathy: time for a reappraisal.

BACKGROUND: Our current immunosuppressive strategies have made little impact on the development of cardiac allograft vasculopathy, the leading cause of long-term allograft loss. This study sought to evaluate the relationship of cellular rejection and immunosuppressive therapy with the development of morbid events resulting from cardiac allograft vasculopathy. METHODS: The study population consisted of 163 consecutive patients who received heart transplants between January 1990 and May 1994. Data regarding nonimmunologic risk factors (lipids, obesity indexes, hypertension, donor age and sex, cytomegalovirus infection, diabetes mellitus, time after transplantation, and cold ischemic time), immunologic factors (histocompatibility, episodes of treated rejection, and average first-year biopsy rejection score), and immunosuppressive regimens (cumulative prednisone dose, average daily prednisone dose, mean cyclosporine level, average cyclosporine daily dose, cumulative azathioprine dose, and average daily azathioprine dose) were collected and analyzed in all patients. The diagnosis of cardiac allograft vasculopathy was established in all patients by a combination of necropsy, angiography, and intravascular ultrasound examination of the allograft vasculature. Cardiac events were defined as sudden death, myocardial infarction, and need for revascularization. RESULTS: Of all variables assembled, stepwise logistic regression recognized cumulative prednisone dose > 15 gm (relative risk [RR] 5.7; p = 0.01), donor age > 35 years (RR 3.73; p < 0.05), and average biopsy rejection score > 1 (RR 2.77; p < 0.05) as independent adverse predictors of cardiac events. In distinction, average daily cyclosporine dose > 4.5 mg/kg/day was found to confer a protective effect (RR 0.16; p = 0.03). CONCLUSIONS: The development of cardiac events as a result of cardiac allograft vasculopathy is influenced by the interdependence of allograft rejection and the balance of immunosuppression. The clinical implications of these findings point to the need for a reappraisal of our traditional approach to using corticosteroids (acute and maintenance) and cyclosporine (maintenance) in heart transplantation.

Adult↗
PubMed1997

Mechanisms of hypertension in cardiac transplantation and the role of cyclosporine.

The use of cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Several mechanisms, including endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in nitric oxide, and altered cytosolic calcium translocation, have been proposed to underlie cyclosporine-induced hypertension. In addition, other studies have shown activation of the sympathetic nervous system and the renin-angiotensin system, as well as abnormalities in prostaglandin metabolism, as culpable mechanisms. Hemodynamic features of cyclosporine-induced hypertension consist of elevated peripheral vascular resistance, ventricular vascular uncoupling contributing to left ventricular hypertrophy, and abnormalities in the diastolic function of the allograft. Combined calcium-channel blockers and angiotensin-converting enzyme inhibitors have been used for this treatment of this clinical problem, and they achieve blood pressure control in 65% of patients. Moreover, these agents may also be beneficial in preventing development of cardiac allograft vasculopathy, a long-term nemesis in cardiac transplantation.

Animals↗
PubMed1996

Adenovirus-mediated in vivo gene transfer in a rabbit model of allograft vasculopathy.

BACKGROUND: The long-term success of heart transplantation continues to be in jeopardy because of the development of accelerated vascular myointimal proliferation. Transfer of genes encoding products that can modulate the adverse consequences of phenomena that cause myointimal proliferation, into the allograft vessel wall, may modify these pathologic processes. The purpose of this study was to assess the feasibility of gene transfer and to evaluate the duration of gene expression in a rabbit heterotopic aortic transplant model of allograft vasculopathy. METHODS: The abdominal aortas of 32 outbred New Zealand rabbits were harvested and cross-sectionally bisected (n = 64). Six donor and recipient animals were used in a preliminary study to examine neointimal proliferation without accompanying gene transfer. Of the remaining 26 rabbits (52 allografts), one half of each allograft aorta was administered a control solution, while the other half was incubated with a replication-defective, recombinant, adenoviral vector-encoding, cytomegalovirus promoter-regulated beta-galactosidase. After a 20-minute incubation period, bilateral aorto-carotid transplantations were performed in 26 recipient rabbits. All animals received cyclosporine immunosuppression (10 mg/kg/day subcutaneously). The allografts were harvested at 3, 7, 10, 21, and 28 days after transplantation and assayed for beta-galactosidase activity. RESULTS: Neointimal areas showed an initially slow increase for the first 10 days, followed by a rapid increase up to 21 days, and tended to plateau thereafter. Significant beta-galactosidase was apparent in aortic sections dissected from host rabbits for all time points, except at 28 days. At the 21-day time point, the aortic section from one rabbit was positive, whereas the other two remained negative. However, the one positive section showed intense beta-galactosidase activity, suggesting variability in the experimental model. At 28 days, all aortic sections were negative. CONCLUSIONS: Our findings confirm that genes delivered by this method are expressed for the duration of early rapid intimal proliferation in this heterotopic rabbit model of aortic allograft vasculopathy. These findings suggest that this animal model can be used to assess the therapeutic potential of gene transfer at the time of vascular transplantation and may provide a novel therapeutic approach to prevent or ameliorate the genesis of allograft vasculopathy.

Adenoviruses, Human↗
PubMed1995

Predictive model to assess risk for cardiac allograft vasculopathy: an intravascular ultrasound study.

OBJECTIVES: This study was performed to assess the influence and interdependence of immunologic and nonimmunologic risk factors in the development of cardiac allograft vasculopathy. Another primary objective was to establish a clinically useful model for risk assessment of cardiac allograft vasculopathy that would facilitate identifying those heart transplant recipients likely to have severe intimal proliferation and thereby at greater risk for adverse clinical events. BACKGROUND: To our knowledge, no comprehensive intravascular ultrasound study has assessed the relative influences of both nonimmunologic and immunologic factors in the development of cardiac allograft vasculopathy, currently the major limitation to long-term cardiac allograft survival. METHODS: Using a computer-assisted model of stepwise logistic regression, immunologic and nonimmunologic risk factors were evaluated to help identify the development of severe intimal thickening in 101 subjects who underwent intravascular ultrasound. Prospective validation of the findings was performed in a separate consecutive cohort of 37 heart transplant recipients, and the accuracy of this model to predict a relative risk > 1 for the development of severe intimal hyperplasia was assessed. RESULTS: Significant independent predictors of severe intimal hyperplasia in this model included a donor age > 35 years, a first-year mean biopsy score > 1 (a measure not only of severity of rejection, but also of frequency of insidious rejection) and hypertriglyceridemia at two incremental levels of risk (150 to 250 mg/dl [1.70 to 2.83 mmol/liter] and > 250 mg/dl [2.83 mmol/liter]). Based on the absence (0) or presence (1) of these factors, 12 individual categories of risk were ascertained with increasing relative risks and predicted probabilities for severe intimal hyperplasia. Prospective validation of this model revealed a sensitivity and specificity of 70% and 90%, respectively, and the positive and negative predictive values were 85% and 80%, respectively. Additionally, subjects with severe intimal thickening had a four-fold higher cardiac event rate than those without severe intimal proliferation on intravascular ultrasound. CONCLUSIONS: This study establishes a clinically useful predictive model that can be applied to individual heart transplant recipients to assess their risk for developing significant cardiac allograft vasculopathy and, thus, aids in the identification of patients at risk for cardiac events in whom closer surveillance and risk factor modification may be warranted.

Adult↗
PubMed1995

Retroviral suicide vector does not inhibit neointimal growth in a porcine coronary model of restenosis.

We attempted to attenuate neointimal formation following vascular injury using a retroviral suicide vector. Epicardial coronary arteries of adult miniature swine were injured by deployment of oversized tantalum stents. One week later, injured segments were exposed to packaged retroviral constructs with or without the herpes simplex virus thymidine kinase gene. Ganciclovir treatments were initiated 48 hours later in both control and experimental swine and continued for two weeks. Four weeks following vascular injury, both control and experimental arteries were harvested and histologically prepared for image analysis. Despite adequate marker gene expression, there was no significant difference in the neointimal area or neointimal/media ratio between control and experimental groups. While the HSVtk ganciclovir system attenuates cell proliferation in other systems, retroviral vector targeting of vascular smooth muscle cells for elimination may be too inefficient to prevent restenosis following angioplasty.

Animals↗