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Biomedical subjects

B Radovancevic

Publications and source records attributed to B Radovancevic.

At least 91 records · Page 5Linked to original sources

Cardiac transplantation: current results at the Texas heart institute.

The first series of cardiac transplants at the Texas Heart Institute began in May of 1968 but was discontinued because of the complications of infection and rejection. A second series of cardiac transplants was initiated in July of 1982 after the introduction of the immunosuppressant drug, cyclosporine. By August of 1984, 30 patients had undergone orthotopic cardiac transplantation for end-stage cardiac disease. Of the patients in this series, four have died of rejection, two of infectious complications, and one of an unknown cause. The remainder have all returned to Class I New York Heart Association (NYHA) cardiac status. All patients were reviewed in detail for suitability of cardiac transplantation and presented to a cardiac transplant review board. All transplanted patients were functional Class IV. Donor hearts were obtained locally or by long-distance procurement. Ten of the hearts were obtained from an average distance of 250 miles from Houston. Donors ranged in age from 16 to 37 years. Requirements were normal cardiac function with minimal use of inotropic support, no history of cardiac disease, absence of cardiac arrest and absence of active infection. Although only one of the patients in the initial group of transplants survived 1 year, to date there have been 11 survivors for more than 1 year in the current series. Advances in cardiac transplantation have resulted in an improved prognosis for the terminal cardiomyopathic patients requiring transplantation. The use of cyclosporine, an immunosuppressant that spares the nonspecific immune system, has been helpful in allowing patients to survive infections. The use of the drug must be carefully monitored, however, because of its numerous toxicities.

Journal Article↗

Mechanical circulatory support for perioperative donor heart failure.

Perioperative acute donor heart failure can be caused by various factors, such as recipient pulmonary hypertension, marginal donor heart function, or immunologic mismatch. Of 265 patients who underwent orthotopic transplantation, four received mechanical support for acute perioperative donor heart failure. In two patients with reactive pulmonary hypertension, right heart bypass (RHB) with a centrifugal pump was used for 53 and 36 hr, respectively. One patient who experienced biventricular donor heart failure was supported for three days with an intraarterial, transvalvular, axial-flow left ventricular assist device (LVAD). Circulation was supported effectively with the LVAD, despite an initial absence of right ventricular function. The fourth patient, who had signs of heart failure, received intraaortic balloon pump support for 24 hr after transplantation. All four patients were weaned from circulatory support, and heart function was restored in each; the mean left ventricular ejection fraction was 63% (range from 57 to 71%). One patient died of fungal infection 14 days after being weaned from pump support, another died of lymphoma two months after support was discontinued, and the remaining two patients are well 9 and 18 months after transplantation. In cases of acute donor heart dysfunction, temporary mechanical assistance is a reliable option for supporting the circulation during heart recovery.

Adult↗

The effect of prolonged left ventricular support on myocardial histopathology in patients with end-stage cardiomyopathy.

To determine the histopathologic effect of prolonged (> 30 days) left ventricular unloading on the myocardium, the authors studied myocardial tissue specimens from eight men (mean age, 40.8 years) with end-stage cardiomyopathy (six idiopathic, two ischemic) who were supported with the HeartMate (Thermo Cardiosystems, Inc., Woburn, MA) left ventricular assist device (LVAD) as a bridge to cardiac transplantation. The average length of support was 79.6 days (range, 31-136 days). Before left ventricular support was instituted, transthoracic echocardiography revealed that all patients had significantly dilated left ventricular cavities (average left ventricular diastolic dimension, 7.2 cm). Tissue specimens from the core of the left ventricular apex, which is removed at the time of LVAD implantation, were compared through pathologic examination with specimens from the explanted hearts at the time of cardiac transplantation. Apical core specimens from all patients exhibited extensive areas of attenuated myocardial fibers, combined with wavy patterns in some areas. In these regions, the nuclei of the cardiac myocytes from idiopathic cardiomyopathy specimens were neither pyknotic nor disappearing, as was noted in an infarcted area of a specimen from one patient with ischemic cardiomyopathy. At the time of heart transplantation, myocardial tissue specimens from the explanted hearts had a significant decrease or disappearance of stretched fibers. There was also a slight increase in interstitial replacement fibrosis, as well as an increase in the diameter of the myocardial fibers. These findings appear to correlate with the clinical impression of improved native ventricular function and with radiographic findings and decreased chamber size during prolonged ventricular support.

Adult↗

Human intraperitoneal response to a left ventricular assist device with a Ti-6AI-4V alloy surface.

The soft tissue reaction to long-term implantation of an intraperitoneal left ventricular assist device (LVAD) was investigated. The HeartMate 1000 (Thermo Cardiosystems, Inc., Woburn, MA) is a pneumatically driven blood pump with smooth titanium alloy (Ti-6AI-4V) outer surfaces that is placed intraperitoneally in the left upper quadrant and sutured to the anterior abdominal wall. It is being used currently as a bridge to cardiac transplant, which sometimes requires extended support times. We examined the tissue capsule that formed around the rigid circular pump housing of four LVADs (duration of implant: 61, 86, 128, and 153 days) for gross, histologic, immunohistochemical, and ultrastructural analysis. Immunostaining was performed using monoclonal and polyclonal antibodies against cytoskeletal tissue markers (vimentin, desmin, alpha-smooth muscle actin), T and B lymphocytes, carcinoembryonic antigen, factor VIII, and cytokeratins (CAM 5.2 AE1/AE3, 34 beta E12, and 35 beta H11). Direct fluorescent immunolabeling for fibrinogen was also performed to characterize cell and tissue type. Histologic analysis of the 3 to 4 mm thick capsule with white, glistening inner surfaces showed fibrovascular tissue with multipotential subserosal cells (MSCs), capillary endothelium, collagen, and a few mononuclear infiltrates. The immunohistochemical profile of the MSCs differed from myofibroblasts despite a morphologic similarity. Transmission electron microscopy revealed abundant rough endoplasmic reticulum and peripherally arranged myofilaments within the spindle shaped cells. It was hypothesized that capsule formation was initiated by fibrin deposition, followed by proliferation of MSCs and subsequent formation of fibrovascular tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Exercise capacity recovers slowly but fully in patients with a left ventricular assist device.

Left ventricular assist devices (LVAD) are used increasingly as bridges to cardiac transplantation. The typical LVAD candidate is a bedridden, critically ill, New York Heart Association (NYHA) Class IV patient with congestive heart failure (CHF) who is dependent upon intravenous, inotropic, and, in many cases, intra-aortic balloon support. The LVAD provides the potential for pre transplant rehabilitation by allowing the patient to become ambulatory, and by improving muscle tone, muscle mass, and nutritional status before transplantation. However, whether the abnormal exercise capacity of these patients improves after implantation has not been elucidated. The purpose of the present study was to evaluate the exercise capacity of patients with CHF after LVAD implantation (n = 10) using peak oxygen consumption during maximal exercise (MVO2), and comparing the results with those of a group of NYHA Class III patients with CHF (n = 14). After 2 months of implantation, MVO2 of the patients with LVAD was 12.8 +/- 0.3 ml/kg/min, which was comparable to that of the NYHA Class III patients with CHF (12.5 +/- 0.5 ml/kg/min). Four of 10 patients with LVAD were monitored for more than 5 months when MVO2 rose to 15.4 +/- 1.0 ml/kg/min (p < 0.05 vs NYHA Class III). In conclusion, the exercise capacity of patients with LVAD recovers slowly but significantly after 5 months of implantation, promising the potential for complete recovery from heart failure in patients supported with an LVAD.

Adult↗

A comparison between intraperitoneal and extraperitoneal left ventricular assist system placement.

The HeartMate left ventricular assist system (LVAS) is being used with increasing frequency as a bridge to heart transplantation and for long-term support of chronic heart failure patients who are not transplant candidates. The surgical techniques and anatomic placement of the HeartMate are factors in minimizing complications that occur during long-term use. Device related bleeding, infection, and other intraabdominal complications are serious adverse events associated with the position of the LVAS. Clinical data from 48 HeartMate supported patients were analyzed retrospectively to determine differences in serious complication rates between intraperitoneal (IP) and extraperitoneal (EP) LVAS placement. The LVAS was placed IP in 37 patients (77%) and EP in 11 patients (23%). The occurrence of postoperative bleeding that required reoperation was 57% in the IP group and 64% in the EP group. Device related bleeding was 8% in the IP group and 29% in the EP. Neither difference in bleeding rate was statistically significant. The overall infection rate during the entire period of LVAS support was similar between groups (IP, 45.7%; EP, 46.2%; p = 0.25); however, device related infection occurred more often in the EP group (46%; IP, 14%; p = 0.025). All patients who recovered from LVAS implantation experienced mild early satiety, but were otherwise free of intra-abdominal complications. The transplantation rate was 64% for the IP group and 78% for the EP group. IP LVAS placement may offer additional protection against device related infections.

Adult↗

Retrospective analysis of infection in patients undergoing support with left ventricular assist systems.

Infection is a problem in patients undergoing support with left ventricular assist systems. To better understand the nature of this problem, we retrospectively analyzed data on 56 patients supported by the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system. Infection was defined as fever > 38 degrees C, white blood count > 12,000 cells/ml, and a need for antimicrobial therapy. Of the 56 patients, 25 (41%) had an infection. Device related infections (as determined by positive culture from driveline, housing, or inflow or outflow tract) occurred in eight patients (14.3%). The most common sites of infection were the respiratory system (42.4%), the central venous catheter (27.8%), and blood (18.3%). Of the positive cultures, 84% were bacterial and 16% fungal. There were no positive viral cultures. Positive cultures from left ventricular assist system related sites made up only 8.7% of the total. All but one of the patients with device related infections survived to transplantation. The long-term survival rate for patients in this group after transplantation was 77.8%. Two patients required surgical revision of the driveline because of infection. Both were free of infection postoperatively. Patients who stayed in the intensive care unit for longer periods had a greater risk of infection (uninfected, 35 days; infected, 78 days). In conclusion, although infection is a problem in patients undergoing support with left ventricular assist systems, it does not preclude survival to transplantation or alter the survival rate after transplantation.

Adolescent↗

Neurohormonal changes after implantation of a left ventricular assist system.

In patients with left ventricular dysfunction, neurohormonal levels are valuable indicators of the severity of heart disease and prognosis. For patients with severe left ventricular dysfunction, left ventricular assist systems (LVAS) are effective as short-term bridges to heart transplantation and are currently being investigated for long-term use. Unknown, however, are the effects of mechanical unloading of the left ventricle on neurohormone levels during the initial weeks after LVAS implantation, and whether these changes are similar to the neurohormonal level decreases observed after cardiac transplantation. This study was undertaken to determine the effect of LVAS support on plasma norepinephrine (PNE) levels during the initial weeks after device implantation. The PNE levels in five consecutive patients with left ventricular dysfunction were measured within 1 week after LVAS implantation and every week thereafter for 5 weeks. Significant decreases in PNE levels were observed after 3 weeks of LVAS support. After 5 weeks of LVAS support, PNE levels had decreased to near normal. For patients with severe left ventricular dysfunction, the improved prognosis after LVAS support may be due in part to the normalization of neurohormonal levels. The findings indicate that PNE levels may be of value in determining whether a patient can be weaned from LVAS support.

Aged↗

Infection and thrombosis in total artificial heart technology: past and future challenges--a historical review.

On the basis of animal testing and a single clinical implant during the 1960s, development of the total artificial heart (TAH) began in earnest in the 1970s. The goal was to produce a pump that could treat biventricular heart failure or any other condition that necessitated removal of the patient's native heart. The early TAHs were pneumatically powered, with externalized drivelines. After undergoing in vivo evaluation in hundreds of sheep and calves at several centers (mainly the Utah Heart Institute), these pumps were implanted in humans, initially for permanent cardiac replacement and later for bridging to transplantation. In both the in vivo experimental setting and the clinical setting, infection and thrombosis were problematic, infection being encountered much more frequently than thrombosis in clinical cases. To minimize these problems, four research groups, funded by NIH, began in 1988 to develop permanent, transcutaneously powered, totally implantable, electromechanical TAHs. For the first time, TAH technology was able to minimize infection and thrombosis, as confirmed by current in vivo studies. These new TAHs will undergo preclinical, pre-IDE studies this year and clinical trials in the near future. This article briefly reviews the evolution of TAH technology, with an emphasis on the prevention and management of infection and thrombosis.

Animals↗

Difficult cases in heart failure: Effective treatment of severe acute myocarditis with intravenous immune globulin and pulse corticosteroids in a 32-year-old patient.

We describe a 32-year-old patient with acute myocarditis resulting in severe heart failure with hemodynamic compromise who improved significantly after treatment with immune globulin and pulse steroids. Six weeks after termination of the immunosuppressive therapy the patient developed symptoms of heart failure again and his ejection fraction decreased to 30%-34%. Treatment with immune globulin resulted in resolution of symptoms and return of left ventricular function. (c)2000 by CHF, Inc.

Journal Article↗

Leishmaniasis in a heart transplant patient.

Infection is a well-recognized complication of immunosuppressive therapy. We describe a case of leishmaniasis in a 62-year-old man who was undergoing immunosuppressive therapy because of heart transplantation. A geologist and native Texan, the patient had traveled extensively in south-central Texas, but not outside of the continental United States. Cutaneous lesions of the extremities developed, which were diagnosed histologically as leishmaniasis and confirmed by means of transmission electron microscopy. Cultures grew Leishmania mexicana. Treatment with sodium antimony gluconate was successful in healing the infective lesions.

Animals↗

Reevaluation of steroid tapering after steroid pulse therapy for heart rejection.

A retrospective analysis was conducted to determine the efficacy and complications resulting from steroid pulse therapy, with or without a steroid taper, in 93 episodes of heart transplant rejection that occurred in 72 patients (58 men, 14 women; mean age, 47.6 years). Each rejection episode was classified according to severity (Texas Heart Institute endomyocardial biopsy scale) and the treatment. Group 1 included 25 episodes of grade 7, 8, 9, or 10 rejection (International Society for Heart Transplantation [ISHT] grade IIIB or IV) that were treated with high-dose methylprednisolone (2.5 to 3.0 gm) and a steroid taper of 1.75 gm over 30 days. Group 2 included 16 episodes of rejection, with the severity of rejection and methylprednisolone pulse therapy being similar to that in group 1, but without a steroid taper. The results of treatment in group 1 were compared with those in group 2. Group 3 included 12 episodes of grade 5, 6, or 7 rejection (ISHT grade IIIA or IIIB) that were treated with moderate-dose methylprednisolone (1.0 to 2.0 gm) and a steroid taper, as described. Group 4 included 40 episodes of rejection, with the severity of rejection and methylprednisolone therapy being similar to that of group 3, but without a steroid taper. The results of treatment in group 3 were compared with those in group 4. No statistically significant differences were found among the groups regarding subsequent episodes of rejection or infection within 3 months of treatment. No statistically significant difference was noted among the groups in the number of rejection episodes requiring additional therapy to control the rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Neurologic complications of heart transplantation in children.

Neurologic complications can add significant morbidity to otherwise successful orthotopic heart transplantations in children. Complications have been reported to occur in up to 50% of children undergoing heart transplantation. The purpose of this study was to identify the prevalence and outcome of neurologic complications of heart transplantation in children. We reviewed all children who received orthotopic heart transplantation at Texas Children's Hospital from November 1984 to November 1990. Twenty-two patients (ages, 3 weeks to 17 years; mean, 8.5 years) underwent heart transplantation using cardiopulmonary bypass with moderate hypothermia. For analysis, we compared results during the first 3 years of our experience, 1984 through 1987 (group 1), to 1987 through 1990 (group 2). Survival was 45% (5 of 11 patients) for group 1 and 73% (8 of 11 patients) for group 2. A neurologic complication was defined as a change in the neurologic examination and/or status. Neurologic complications included seizures (6 of 22 patients), strokes (3 of 22 patients), unresponsiveness (3 of 22 patients), and change in mental status (2 of 22 patients). Early (within 2 weeks after operation) neurologic complications occurred in 45% (10 of 22 patients), were persistent (sequelae lasting more than 4 months) in 27% (6 of 22 patients), and resulted in death in 9% (2 of 22 patients). Late (after 2 weeks after operation) neurologic complications occurred in 23% (5 of 22 patients), were persistent in 9% (2 of 22 patients), and have occurred in only two survivors. Neurologic factors were not responsible for the cause of death in group 2. No neurologic complications (early or late) were seen in 1 of 11 patients in group 1 as compared with 7 of 11 patients in group 2 (p < 0.015). Serious neurologic morbidity decreased between the two groups after preoperative cyclosporine was avoided and postoperative hypertension was controlled. All survivors are functioning at age-appropriate levels. Although neurologic complications may be frequent, long-term neurologic disability in survivors is rare.

Adolescent↗

Long-term results in diabetic patients undergoing heart transplantation.

We conducted a retrospective study of 305 nondiabetic patients and 37 diabetic patients who underwent heart transplantation from July 1982 to May 1990. Actuarial survival was similar for both groups of patients at 1 year (76.4% versus 81.3%) and at 2 years (69.6% versus 73.0%). Because we were interested in long-term results, we further analyzed only those patients surviving more than 1 year after transplantation (214 nondiabetic patients and 29 diabetic patients). Mean follow-up for the nondiabetic patients was 31.8 +/- 16.2 months and for the diabetic patients, 32.9 +/- 4.1 months. The respective mean age in each group was 50.4 +/- 10.3 years and 51.6 +/- 9.1 years. No difference was observed between the nondiabetic patients and diabetic patients regarding the rejection rate per patient-month (0.040 +/- 0.041 versus 0.045 +/- 0.051 episodes per patient-month), the infection rate per patient-month (0.056 +/- 0.081 versus 0.081 +/- 0.102 episodes per patient-month), or renal function as evidenced by mean creatinine levels at 1, 2, and 3 years. Twelve patients were insulin-dependent before transplantation; and 1 year after transplantation, they required an insulin dose 2.12 times greater than the dose before operation. Coronary artery disease developed in 32.8% of the nondiabetic patients, compared with 31.0% of the diabetic patients by the fourth year of follow-up. Despite the need for increased insulin doses, the diabetic patients had similar long-term survival to that of the nondiabetic patients, without an increased risk of rejection, infection, renal dysfunction, or coronary artery disease. Our experience supports the feasibility of heart transplantation in selected diabetic recipients.

Adult↗

Heart transplantation after mechanical circulatory support: four years' experience.

To determine the effect of mechanical circulatory support before heart transplantation, we conducted a retrospective analysis of 207 men who underwent staged orthotopic transplantations. Of these patients, 185 (group I) required pharmacologic support before transplantation; 14 (group II) required mechanical circulatory support with an intraaortic balloon pump (duration of support, 1 to 26 days); and eight (group III) required advanced mechanical circulatory support with an implantable left ventricular assist device (duration of support, 19 to 132 days). A comparison of complications after transplantation (infection and rejection), hospitalization, and survival showed that no significant differences existed among the three groups. In each group, respectively, 1-year survival was 80.9%, 77.3%, and 75%, and 2-year survival was 75.7%, 67.7%, and 75%. Based on our experience, patients receiving mechanical circulatory support before transplantation can be expected to have a good outcome. In fact, such support can help to improve their end-organ perfusion, and, thus, their status as heart transplantation candidates. Furthermore, this study shows that advanced mechanical circulatory support is possible even for prolonged periods, with low risk of sudden death. This finding is an important step toward development of a permanent assist device.

Adult↗