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Biomedical subjects

R C Bourge

Publications and source records attributed to R C Bourge.

At least 37 records · Page 2Linked to original sources
PubMed1998

A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators.

BACKGROUND: Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity. METHODS: We enrolled 3833 patients who had symptoms of New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 30 percent or less despite optimal treatment. The mean follow-up was 286 days. RESULTS: There were significantly fewer deaths in the placebo group (242 deaths, or 18.9 percent) than in the 60-mg vesnarinone group (292 deaths, or 22.9 percent) and longer survival (P=0.02). The increase in mortality with vesnarinone was attributed to an increase in sudden death, presumed to be due to arrhythmia. The quality of life had improved significantly more in the 60-mg vesnarinone group than in the placebo group at 8 weeks (P<0.001) and 16 weeks (P=0.003) after randomization. Trends in mortality and in measures of the quality of life in the 30-mg vesnarinone group were similar to those in the 60-mg group but not significantly different from those in the placebo group. Agranulocytosis occurred in 1.2 percent of the patients given 60 mg of vesnarinone per day and 0.2 percent of those given 30 mg of vesnarinone. CONCLUSIONS: Vesnarinone is associated with a dose-dependent increase in mortality among patients with severe heart failure, an increase that is probably related to an increase in deaths due to arrhythmia. A short-term benefit in terms of the quality of life raises issues about the appropriate therapeutic goal in treating heart failure.

Aged↗
PubMed1998

Gene polymorphisms for plasminogen activator inhibitor-1/tissue plasminogen activator and development of allograft coronary artery disease.

BACKGROUND: Impaired fibrinolytic activity has been linked to the presence and severity of allograft vasculopathy (Tx CAD). This impairment may be associated with the presence of certain fibrinolytic protein gene polymorphisms. METHODS AND RESULTS: To investigate the relation between donor-specific fibrinolytic protein genotypes and Tx CAD, we identified donor plasminogen activator inhibitor-1 (PAI-1) HindIII and tissue plasminogen activator (TPA) EcoRI restriction fragment length polymorphisms-based genotypes by Southern blot analysis in 48 recipients of cardiac allografts and correlated these genotypes with the development of CAD. No association was found between donor TPA genotypes and the presence of Tx CAD. Among the 48 patients, 17% were homozygous for the 1/1 PAI-1 genotype, 51% for the 2/2 PAI-1 genotype, and 32% for the 1/2 PAI-1 genotype. The actuarial freedom from any CAD for the recipients with each respective donor PAI-1 genotype at 12 and 24 months was 100% and 100% for the 1/1 PAI-1 genotype, 92% and 92% for the 1/2 PAI-1 genotype, and 75% and 45% for the 2/2 PAI-1 genotype (P=0.03). Recipients with a diseased 2/2 PAI-1 genotyped allograft had longer ischemic times (P=0.02) than those recipients with a Tx CAD-free allograft. CONCLUSIONS: These data suggest that recipients with a 2/2 PAI-1 genotype are at a significant risk of developing Tx CAD. This genotype may serve as a useful screening tool for predicting the future development of Tx CAD.

Adult↗
PubMed1998

Evaluation of hibernating myocardium in patients with ischemic heart disease.

Patients with ischemic heart disease and significant left ventricular dysfunction are often difficult to manage medically. Revascularization procedures may improve left ventricular function and prognosis in this population if hypocontractile yet viable myocardium (hibernating myocardium) is demonstrated. Nuclear cardiology studies (single photon and positron methods), two-dimensional echocardiography, and magnetic resonance imaging studies have been utilized to identify hibernating myocardium. If thallium-201 studies are performed, the use of reinjection of thallium and repeat imaging improves the sensitivity of these studies for the detection of viable myocardium. Dobutamine echocardiographic studies may have a higher specificity and positive predictive value for the subsequent improvement of regional systolic left ventricular function after revascularization than the nuclear techniques. However, thallium studies have an excellent negative predictive value. Positron emission tomography (PET) allows the simultaneous assessment of perfusion and metabolic activity; however, these studies are expensive and not widely available. Functional evaluation with PET is in its infancy. Functional cardiac magnetic resonance imaging (MRI), although not widely available yet, provides the most accurate evaluation of regional ventricular function. MRI spectroscopy may be utilized to assess myocardial viability. As acquisition times improve and "real-time" imaging becomes a reality, MRI and MRI spectroscopy will likely become very accurate tools for assessing functional reserve and metabolic activity. The selection of the most appropriate method for assessment of myocardial viability will include consideration of a patient's characteristics, the presence of coronary arterial tree amenable to revascularization techniques, the techniques available to the clinician to assess viability, and local revascularization experience in this population. The result of an individual patient's evaluation is relevant to the consideration of coronary revascularization, or if this is not possible, cardiac transplantation.

Echocardiography↗
PubMed1998

Intrapulmonary shunting in primary pulmonary hypertension: an observation in two patients treated with epoprostenol sodium.

Continuous intravenous infusion of epoprostenol sodium in selected patients with primary pulmonary hypertension improves symptoms and survival. This report describes two patients with primary pulmonary hypertension treated with epoprostenol in whom intrapulmonary shunting and severe hypoxemia occurred. Intrapulmonary shunting was confirmed by contrast echocardiography showing delayed appearance of bubbles in the left cardiac chambers after peripheral venous injection of agitated saline solution.

Antihypertensive Agents↗
PubMed1998

Risk of death or incapacitation after heart transplantation, with particular reference to pilots.

Pilots who have received a heart transplant may subsequently want to resume flying. This study was undertaken to determine whether a group of heart transplant recipients who had a particularly low risk of sudden unexpected death could be identified from clinical data. An event, "rapid-onset death," was defined incorporating a number of possible causes of death that could result in a heart transplant recipient-pilot losing control of an airplane. The survival of 3676 patients undergoing a first heart transplantation was 85% and 73% at 1 and 5 years, respectively, the hazard function having a high early phase of risk. When time zero was moved to the beginning of the second year after transplantation, the freedom from "rapid-onset death" at posttransplantation year 2 and posttransplantation year 5 was 96.8% and 88%, respectively. For patients who had both a "normal" coronary angiogram and no episodes of acute heart rejection during the first year transplantation, the probability of "rapid onset death" during the second posttransplantation year was 1.4%, and given the same circumstances, during the third posttransplantation year the risk of "rapid-onset death" was 1.6%. This information is potentially useful to the Federal Aviation Administration for policy decisions regarding this issue.

Adolescent↗
PubMed1998

Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database.

BACKGROUND: Controversy exists regarding donor and recipient factors that promote the development and progression of coronary artery disease after heart transplantation and the likelihood of coronary artery disease causing death or retransplantation. METHODS: To investigate this issue in a large cohort of patients, we analyzed 5963 postoperative angiograms performed in 2609 of the 3837 patients undergoing heart transplantation at 39 institutions between January 1990 and December 1994. Coronary artery disease was classified as mild, moderate, or severe on the basis of left main involvement, primary vessel stenoses, and branch stenoses. Coronary artery disease was considered severe if left main stenosis was > 70% or 2 or more primary vessels stenoses were > 70% or branch stenoses were > 70% in all 3 systems. RESULTS: By the end of 5 years after heart transplantation, coronary artery disease was present in 42% of the patients, mild in 27%, moderate in 8%, and severe in 7%. Coronary artery disease-related events (death or retransplantation) had an actuarial incidence of 7% at 5 years and occurred in 2 of 3 of the patients with development of angiographically severe coronary artery disease. By multivariable logistic analysis, risk factors for donor coronary artery disease included older donor age (P < .0001) and donor hypertension (P=.0002). By multivariable analysis in the hazard function domain, risk factors identified for the earlier onset of allograft coronary artery disease included older donor age (P < .0001 ), donor male sex (P=.0006), donor hypertension (P=.07), recipient male sex (P=.02), and recipient black race (P=.01). The actuarial incidence of severe coronary artery disease was 9% at 5 years. CONCLUSIONS: Angiographic coronary artery disease is very common after heart transplantation, occurring in approximately 42% of the patients by 5 years. Older donor age, donor hypertension, and male donor or recipient predict earlier onset of angiographic allograft coronary artery disease. Although severe angiographic allograft coronary artery disease occurs in only 7% of the patients at 5 years, its presence is highly predictive of subsequent coronary artery disease-related events or retransplantation.

Adolescent↗
PubMed1997

Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group.

BACKGROUND: Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationship of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. METHODS AND RESULTS: The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n = 41) or conventional therapy alone (n = 40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. CONCLUSIONS: The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.

Adult↗
PubMed1997

Replacement of an intracorporeal left ventricular assist device.

An intracorporeal left ventricular assist device was placed as a bridge to cardiac transplantation in a 51-year-old man after an acute myocardial infarction. After 126 days of support, the left ventricular assist device malfunctioned. The pump, which had a tear in its pneumatic drive line, was successfully replaced.

Equipment Design↗
PubMed1997

Simultaneous use of an implanted defibrillator and ventricular assist device.

A left ventricular assist device was placed as a bridge to cardiac transplantation in a 51-year-old man with cardiogenic shock. Placement of the left ventricular assist device occurred 5 years after implantation of an implantable cardioverter/defibrillator. The implantable cardioverter/defibrillator discharged appropriately during ventricular assist device support to terminate episodes of sustained ventricular tachycardia without causing malfunction of the ventricular assist device.

Defibrillators, Implantable↗
PubMed1997

Ventricular assist devices as a bridge to cardiac transplantation. A prelude to destination therapy.

OBJECTIVE AND BACKGROUND: Ventricular assist devices (VADs) have been used for temporary circulatory support pending transplantation or recovery of the native heart. Outcome in 38 patients treated at the authors' institution with VADs pending transplantation was analyzed to provide information relevant to the future use of VADs as permanent implants. METHODS: Thoratec (Thoratec Laboratories, Pleasanton, CA) or HeartMate (Thermo Cardiosystems, Woburn, MA) VADs were used in all cases. Patients were considered for VAD placement if they were candidates for cardiac transplantation and fulfilled the criteria for the Food and Drug Administration investigational Device Exemption trials. The following adverse events were included in the analysis; death during VAD support, device malfunction, bleeding, neurologic events, support-related events that preclude transplantation, and device-related infections. Patient survival and complication rates were quantified using the Kaplan-Meier method, competing risk analysis, and hazard functions. RESULTS: Nineteen patients had transplantation. Three patients had VAD removal after cardiac recovery and 16 died without transplantation. The duration of VAD support ranged from 0 to 279 days. The hazard function for death during VAD support had an early phase that lasted for 2 weeks after VAD placement, and early death was related to the preimplant condition of the patient. Device-related infections were noted in 11 patients. Seven of these patients had transplantation after clearing the infection, whereas four died without transplantation. Neurologic events occurred in seven patients. There were no device malfunctions that led to patient death. CONCLUSIONS: The absence of fatal device malfunctions suggests that longer term support with current VAD designs is feasible. Appropriate patient selection, infection control, and avoidance of thromboembolic neurologic complications will be crucial to the success of permanent VAD use.

Adult↗
PubMed1997

Predicting outcome after cardiac transplantations: lessons from the Cardiac Transplant Research Database.

Survival and quality of life after transplantation are limited by posttransplant events such as rejection and infection. The description and subsequent prediction of these and other events is the goal of the Cardiac Transplant Research Database group. This paper provides a description of the purpose, methods of data collection and analysis, and results of the published data from the Cardiac Transplant Research Database. A review of the analyses of death, rejection, and infection is made along with a discussion of the clinical application of these data. Utilizing the data from the Cardiac Transplant Research Database, the clinician may apply established risk factors for posttransplant adverse events to individual patients.

Data Interpretation, Statistical↗
PubMed1997

Competing outcomes after heart transplantation: a comparison of eras and outcomes.

To understand the time relatedness of the various causes of death after heart transplantation, a study was undertaken to examine the relative importance of each of these causes of death across time, as well as between eras. The analysis, which was in the competing outcomes domain, involved 326 patients undergoing primary heart transplantation between November 1981 and June 1994, of which 122 patients died. Two eras were considered--an earlier era (1981 to 1986) and a later era (1987 to 1994). During the later era, the estimated survival rate at 1 year and 5 years was 85% and 69%, respectively. During the first posttransplantation year, patients in the earlier era were three times more likely to die of early graft failure than in the later era, but the difference may have been due to chance (p > 0.2). During the first posttransplantation year, patients were three times as likely to die of acute rejection in the earlier era (p = 0.02). Patients surviving 3 or more years in both eras had a similar (approximately 3%) likelihood of death from coronary artery disease over the ensuing 4 years. In the later era, the risk of dying of malignancy (2.5%), infection (3.2%), or miscellaneous other causes (4.1%) was as likely after 3 years as dying of coronary artery disease (3.2%). Competing outcomes analysis is a useful means of portraying the distribution of multiple time-related causes of death. In the current era, the deleterious long-term effects of immunosuppression (malignancy and infection), as well as coronary artery disease, threaten long-term survival.

Adolescent↗
PubMed1997

The incremental risk of female sex in heart transplantation: a multiinstitutional study of peripartum cardiomyopathy and pregnancy. Cardiac Transplant Research Database Group.

BACKGROUND: Controversy remains regarding the reason females seem to be at increased risk for rejection after heart transplantation. Therefore this study was performed to define the effect of a pretransplantation diagnosis of peripartum cardiomyopathy and the effect of previous pregnancy on the outcome (incidence of rejection and death) of females after heart transplantation. METHODS: In this multiinstitutional study of 3244 adult (greater than 13 years of age) heart transplant recipients, (a) the outcome of 40 females who underwent transplantation for peripartum cardiomyopathy was compared with that of 200 females of childbearing age (13 to 45 years) who underwent transplantation for other indications and (b) the posttransplantation outcome of 543 females with a history of pregnancy was compared with that of 101 nulliparous adult females and 2562 adult males. RESULTS: The posttransplantation outcome of females with a history of peripartum cardiomyopathy was similar to that of females of childbearing age who underwent transplantation for other indications. However, parous females had a significantly shorter time to first rejection (p < 0.0001) and greater cumulative rejection than nulliparous females or males. By multivariable analysis, the risk factors for cumulative rejection at 1 year were a history of pregnancy (p < 0.0001), younger recipient age (p < 0.0001), induction therapy (p < 0.0001), and the number of human leukocyte antigen-DR mismatches (p = 0.007). CONCLUSION: Our data suggest that it is previous pregnancy, and not sex per se, that is associated with an increased frequency of rejection in females after heart transplantation.

Actuarial Analysis↗
PubMed1997

Heart transplant rejection with hemodynamic compromise: a multiinstitutional study of the role of endomyocardial cellular infiltrate. Cardiac Transplant Research Database.

BACKGROUND: The natural history of patients experiencing hemodynamic compromise with rejection has been incompletely characterized. This multiinstitutional study examined the outcome of such episodes, particularly with regard to the extent of cellular infiltrate on the index endomyocardial biopsy. METHODS: From January 1, 1990, through June 30, 1994, 3367 patients in the Cardiac Transplant Research Database experienced 4137 episodes of rejection. Severe hemodynamic compromise occurred in approximately 5% of the rejection episodes, and this proportion remained relatively constant over time. RESULTS: Recipient risk factors for rejection with severe hemodynamic compromise included black race, female recipient sex, and diabetes. The 3-month actuarial survival rate was 60% after rejection with severe hemodynamic compromise versus 95% after rejection with no or mild compromise. Low initial biopsy score conferred a higher early survival, but a lower survival at 2 years after rejection with severe hemodynamic compromise. Among patients who survive an initial rejection episode with severe hemodynamic compromise, survival at 2 years after an episode was 46% among those who had a low initial biopsy score versus 84% with a high biopsy score. CONCLUSIONS: Rejection with hemodynamic compromise, although rare, represents a major complication of heart transplantation with a poor long-term outcome. Survivors of hemodynamically compromising rejection episodes associated with low biopsy scores in the International Society for Heart and Lung Transplantation grading system have a significantly worse long-term outcome than survivors of episodes associated with high scores. These findings suggest that immunologic mechanisms other than lymphocytic infiltration of the cardiac allograft are important and distinct causes of allograft dysfunction.

Actuarial Analysis↗
PubMed1997

Serial measurements of interleukin-6, interleukin-8, tumor necrosis factor-alpha, and soluble vascular cell adhesion molecule-1 in the peripheral blood plasma of human cardiac allograft recipients.

BACKGROUND: Cardiac allograft rejection is largely an inflammatory response that, if allowed to proceed unchecked, will result in hemodynamic compromise or cardiogenic shock. Soluble mediators produced during an inflammatory response could potentially provide information regarding the initiation, progression, and outcome of a rejection episode. To test this hypothesis, we investigated the use of plasma cytokine measurements for interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF alpha) in combination with measurements of soluble vascular cell adhesion molecule-1 (VCAM-1), an adhesion molecule, as a means for the detection of cardiac allograft rejection. METHODS: Serial enzyme-linked immunosorbent assays were performed on plasma samples collected from 29 patients three times per week during the first 8 weeks after transplantation. RESULTS: IL-6 plasma concentrations increased fivefold in the first week after transplantation (p < 0.001 vs pretransplantation levels) and thereafter remained at low levels for the next 6 weeks, with a small increase during the 8 weeks after transplantation (p = 0.006). In contrast, TNF-alpha, IL-8, and VCAM-1 levels remained low during the first 6 weeks after transplantation followed by a rise in mean VCAM-1 levels from 841 +/- 38 to 979 +/- 52 ng/ml at week 8. To determine the relationship of levels of each of the four soluble factors with rejection, the mean values obtained during the time interval 1 to 5 days before rejection were compared to mean values obtained during rejection and at other periods of no rejection (baseline). Cytokine levels were not predictive of rejection (no difference in levels 0 to 5 days before rejection versus baseline, p > 0.3 for IL-6, IL-8, TNF-alpha). However, VCAM-1 levels increased 0 to 5 days before rejection compared with baseline (914 +/- 40 vs 844 +/- 30 ng/ml, p = 0.06). CONCLUSIONS: IL-6 levels are increased immediately after heart transplantation. Circulating IL-6, IL-8, and TNF alpha levels do not predict rejection during the first 8 weeks after transplantation. Soluble VCAM-1 increases within 5 days before rejection and may potentially serve as a noninvasive marker for early rejection.

Adolescent↗
PubMed1996

Secular trends in cardiac transplant recipient and donor management in the United States, 1990 to 1994. A multi-institutional study. Cardiac Transplant Research Database Group.

BACKGROUND: The growth of the US cardiac transplant waiting list has outpaced the increase in donors, resulting in a widening gap between the number of waiting recipients and available donors. These trends have generated concern that longer waiting times may result in more patients deteriorating to urgent status and that transplanting only patients who are in an advanced state of decompensation will reduce posttransplant survival. Furthermore, the shortage of donors may result in extending the guidelines for donor acceptability to a degree that increases graft failure and posttransplant mortality. We measured these secular trends in the Cardiac Transplant Research Database to provide current data on time-dependent changes in US cardiac transplant practice and survival. METHODS AND RESULTS: At the time of this analysis, the Cardiac Transplant Research Database included all 2749 patients transplanted from January 1, 1990, to June 30, 1994, in the 25 participating transplant centers. During this 4.5-year period, the median waiting time for recipients who received a transplant increased from 2.7 to 3.5 months (P < .0001), and the proportion of recipients whose status was urgent at transplantation increased from 41% to 60% (P < .0001). Donor ischemic time increased from 150 to 166 minutes (P < .0001), and the proportion of donors requiring pressor support increased from 68% to 85% (P < .0001). Despite these changes in practice, the 1-year survival rate remained constant at 84% during this 4.5-year interval. There was no significant difference in 1-year survival rate between urgent status patients (83%) and nonurgent status patients (85%) (P = .08). CONCLUSIONS: The widening gap between the number of waiting recipients and the number of donors has resulted in a continuing trend toward transplanting urgent status recipients and to a liberalization of donor acceptance criteria. Despite these changes, posttransplant survival has remained constant.

Adult↗