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Biomedical subjects

Branislav Radovancevic

Publications and source records attributed to Branislav Radovancevic.

At least 37 records · Page 2Linked to original sources
PubMed2005

Chromium supplementation shortens QTc interval duration in patients with type 2 diabetes mellitus.

BACKGROUND: We investigated the potential effects of chromium supplementation on QTc interval duration in type 2 diabetic patients. METHODS: Of 60 patients with type 2 diabetes mellitus, 30 were randomly assigned to group A, and 30 to group B. Group A received 1000 microg of chromium picolinate (CrPic) daily for 3 months, followed by placebo in the next 3 months; group B was treated with placebo for the first 3 months and CrPic in the next 3 months. At each visit, QT interval was measured on a standard electrocardiogram by averaging 3 consecutive beats in leads II and V4 and corrected for heart rate with Bazett formula. RESULTS: Although baseline QTc interval was similar in both groups (422 +/- 34 milliseconds in group A vs 425 +/- 24 milliseconds in group B, P = .77), QTc interval at 3 months was shorter in group A (406 +/- 35 milliseconds) than in group B (431 +/- 26 milliseconds, P = .01). In the following 3 months, QTc interval shortened in group B but not in group A, which resulted in a comparable QTc interval duration of both groups at the end of the study (414 +/- 28 milliseconds in group A vs 409 +/- 22 milliseconds in group B, P = .50). Apart from body mass index (31.4 +/- 4.2 kg/m2 in patients with QTc shortening vs 28.7 +/- 4.2 kg/m2 in patients without QTc shortening, P = .03), none of the clinical and laboratory variables predicted QTc interval shortening in our patient cohort. CONCLUSIONS: Short-term chromium supplementation shortens QTc interval in patients with type 2 diabetes mellitus.

Chromium↗
PubMed2005

Lung cancer after heart transplantation: a 17-year experience.

BACKGROUND: The effects of heart transplantation on lung cancer incidence in heart transplant recipients are unclear. METHODS: In an observational study, we retrospectively reviewed the charts of all patients undergoing heart transplantation at our institution from July 1982 to July 1999. Data on lung cancer incidence, risk factors, treatment, and outcome were collected. RESULTS: Five hundred seventy-two patients (mean age, 50 +/- 11 years; range, 18 to 73) were considered at risk for lung cancer. Of these, 324 (57%) had a more than 20 pack-year history of smoking before transplantation. Lung cancer developed in 2 patients 1 year or less after transplantation and in 8 patients more than 1 year after transplantation (incidence, 2.2 per 1,000 patients per year of follow-up). Non-small cell lung cancer was diagnosed in all cases. Median survival was 10.8 months (range, 2 to 37.5). Routine annual chest radiographs after transplantation enabled early diagnosis in 5 cases (stages Ia and IIa), which correlated with better mean survival (28.1 months [range, 19 to 37.5] versus 5.1 months [range, 2 to 10.8]; p = 0.0002). CONCLUSIONS: The incidence of lung cancer in our population of heart transplant recipients appears to be no higher than in nontransplant populations with similar risk factors (ie, smoking and age). Routine radiographic imaging of transplant recipients may allow earlier detection of lung cancer and thus offer a survival benefit.

Adolescent↗
PubMed2005

Atorvastatin therapy increases heart rate variability, decreases QT variability, and shortens QTc interval duration in patients with advanced chronic heart failure.

BACKGROUND: Although statins decrease the incidence of ventricular arrhythmias in patients with atherosclerotic heart disease, their potential antiarrhythmic effects in heart failure remain undefined. METHODS AND RESULTS: Of 80 heart failure patients enrolled, 40 were randomized to receive atorvastatin (statin group); the remaining 40 served as controls. At baseline and after 3 months, we measured heart rate variability (HRV), QT variability (QTV), and QTc interval using interactive high-resolution electrocardiogram analysis. The 2 groups did not differ in baseline HRV standard deviation of normal-to-normal intervals (SDNN) (RR): 24.6 +/- 2.8 ms in statin group versus 24.8 +/- 3.1 ms in controls, P = .72; square root of the mean of squared differences between successive intervals (rMSSD) (RR): 21.2 +/- 2.7 ms versus 21.7 +/- 2.9 ms, P = .43), QTV SDNN (QT): 6.4 +/- 1.5 ms versus 6.4+/-1.7, P = .96; rMSSD QT): 9.0 +/- 2.4 ms versus 8.7 +/- 2.9 ms, P = .65, and QTc interval 450 +/- 30 ms versus 446 +/- 27 ms, P = .59. At 3 months, the statin group displayed higher HRV SDNN RR): 27.2 +/- 4.9 ms versus 24.4 +/- 2.8 ms in controls, P = .003; rMSSD RR: 24.7 +/- 4.2 ms versus 21.3 +/- 5.6 ms, P = .004, lower QTV SDNN (QT): 5.1 +/- 1.9 ms versus 6.5 +/- 2.1, P = .004; rMSSD (QT): 6.6 +/- 2.8 ms versus 8.8 +/- 3.1 ms, P = .002, and shorter QTc interval 437 +/- 29 ms versus 450 +/- 25 ms, P = .03 than the control group. CONCLUSIONS: Atorvastatin increases HRV, decreases QTV, and shortens QTc interval, and may thereby reduce the risk of arrhythmias in patients with advanced heart failure.

Anti-Arrhythmia Agents↗
PubMed2005

Evaluation of myocardial function in patients with end-stage heart failure during support with the Jarvik 2000 left ventricular assist device.

In 2 patients with the Jarvik 2000 left ventricular assist device (LVAD), we assessed left ventricular systolic function through pressure-volume loops and E(max) at the beginning and end of the support period to potentially predict the possibility of pump removal without transplantation. Immediately before LVAD implantation and explantation, pressure and volume measurements were made with catheters and echocardiography, respectively, the E(max) being calculated from the slope of the pressure-volume loops, and the left ventricular ejection fraction (LVEF) being estimated by echocardiography. Transplantation was performed after 14 and 62 days, respectively, during which the LVEF increased by 75% (from 12% to 21%) in Patient 1 and remained unchanged (from 16% to 18%) in Patient 2, whereas the E(max) increased from 0.63 and 0.42 mm Hg/ml, respectively, to 1.31 and 1.07 mm Hg/ml, reflecting a 107% and 155% improvement. In these 2 cases, the E(max) was a more reliable indicator of intrinsic myocardial contractility than was the LVEF.

Cardiac Catheterization↗
PubMed2005

Factors predicting 10-year survival after heart transplantation.

BACKGROUND: We sought to identify factors predictive of long-term (>10-year) survival in heart transplant (HTx) recipients. METHODS: Four hundred fifteen adult patients underwent HTx at our institution between August 1982 and May 1997. The 158 patients who survived >10 years (Group A) and the 116 patients who died between 2 and 6 years (Group B) of HTx were compared in terms of gender, gender mismatch, ethnicity, age, height, weight, United Network for Organ Sharing status, type of induction therapy (OKT3 or anti-thymocyte globulin), infections (bacterial, viral, fungal and protozoal), cytomegalovirus (CMV) status, CMV mismatch, diabetes mellitus, hypertension and incidence of rejection episodes and transplant coronary artery disease within 2 years of HTx. RESULTS: Group A (135 men, 23 women; mean age 48 +/- 11 years) had significantly fewer post-HTx rejection episodes and viral, bacterial, fungal and total infections than did Group B (95 men, 21 women; mean age 49 +/- 12 years). Group A also had a significantly lower mean donor age, a lower incidence of pre-HTx diabetes, and a lower mean cholesterol level 1 year after HTx. In a multivariate analysis, fewer bacterial infections and rejection episodes after HTx, the absence of pre-HTx diabetes, and lower donor age were associated with longer survival. CONCLUSIONS: Pre-HTx diabetes, donor age and incidences of infection and rejection within 2 years of HTx predict long-term (>10-year) survival. Better control of infection and rejection during the first 2 years after HTx may improve survival.

Age Factors↗
PubMed2005

Fluorescence imaging microscopy of cellular markers in ischemic vs non-ischemic cardiomyopathy after left ventricular unloading.

BACKGROUND: The heart undergoes repair and initiates protective mechanisms via ventricular unloading. We examined the presence of 2 markers in pre-unloaded and post-unloaded human cardiac tissue that are important indicators of cardiac failure, tumor necrosis factor-alpha and inducible nitric oxide synthase. We also measured 2 nuclear transcription factors, NFkappaB50 and NFkappaB65, comparing quantities and localizations to determine if mechanical unloading reduced their presence, as these markers are also thought to be indicators of impending heart failure. Amounts and localizations in patients that had been diagnosed with either ischemic or non-ischemic cardiomyopathy were compared after mechanical unloading with a left ventricular assist device. To establish that unloading had been achieved, levels of atrial natriuretic protein were determined. METHODS: Core biopsies were harvested at assist device implantation and removal. Fluorescence deconvolution microscopy image reconstructions of fluorescence probes were correlated with data obtained by western Blot and electrobility shift assays. RESULTS: Statistically significant differences in localization and amounts of tumor necrosis factor and nitric oxide synthase were seen between pre- and post-assist device samples. Amounts of tumor necrosis factor and nitric oxide synthase in ischemic tissue were increased at the time of assist device removal, but decreased in dilated or idiomyopathic samples. Ventricular unloading resulted in reduced levels of natriuretic protein, with the greatest reduction being seen in ischemic tissue. Both NFkappaB50 and NFkappaB65 increased in ischemic tissue, but only NFkappaB50 in non-ischemic samples. CONCLUSIONS: Changes in localization of the factors and altered levels of cytokine and nitric oxide synthase indicate that the heart switches to a "protective and repair" mode, and mechanical unloading allows this transition to occur. Observed changes were dependent on the etiology of the disease.

Atrial Natriuretic Factor↗
PubMed2005

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.

Adult↗
PubMed2005

Nitric oxide versus prostaglandin E1 for reduction of pulmonary hypertension in heart transplant candidates.

BACKGROUND: We sought to directly compare the effects of prostaglandin E1 (PGE1) and nitric oxide (NO) in testing for pulmonary hypertension reversibility in heart transplant candidates. METHODS: We included 19 heart transplant candidates who fulfilled at least 1 of 3 criteria: pulmonary vascular resistance (PVR) of >4 Wood units; transpulmonary gradient (TPG) of >12 mmHg; or systolic pulmonary artery pressure (PAP) of >60 mmHg. Patients randomly received either PGE1 (0.05, 0.2 and 0.5 microg/kg/min) or NO (40, 60 and 80 ppm) and were crossed-over to the second medication after receiving the maximal dose of the first. RESULTS: With PGE1, TPG decreased by 21% (baseline 20.3 +/- 6.8 mmHg; final 16.0 +/- 7.0 mmHg) compared to a 34% decrease with NO (baseline 20.8 +/- 6.2 mmHg; final 13.8 +/- 5.4 mmHg) (p = 0.13). PVR decreased by 42% with PGE1 (baseline 6.2 +/- 4.0 Wood units; final 3.6 +/- 1.8 Wood units) and by 47% with NO (baseline 6.0 +/- 3.9 Wood units; final 3.2 +/- 1.6 Wood units) (p = 0.87). Mean systemic pressure decreased with PGE1 (baseline 76.1 +/- 10.5 mmHg; final 69.4 +/- 12.2 mmHg; -9%) but not with NO administration (baseline 70.2 +/- 14.7 mmHg; final 71.6 +/- 10.9 mmHg; +2%) (p = 0.01). TPG was lowered to <12 mmHg in 14 patients. Of these, 6 (46%) responded to both PGE1 and NO, 4 (27%) responded only to PGE1, and 4 (27%) responded only to NO. CONCLUSIONS: The effects of PGE1 and NO on pulmonary hypertension are comparable, with PGE1 having more systemic hypotensive effects. Due to variability of patient responses, we recommend multiple rather than single-agent pharmacologic testing for the reversibility of pulmonary hypertension.

Administration, Inhalation↗
PubMed2005

Survival, graft atherosclerosis, and rejection incidence in heart transplant recipients treated with statins: 5-year follow-up.

BACKGROUND: Few studies have examined the long-term benefits of statin treatment in heart transplant recipients. METHODS: In this observational study, we retrospectively reviewed data pertaining to 5-year follow-up of patients who underwent heart transplantation between 1993 and 1996 and who survived the first 30 days after transplantation. Patients were assigned to groups according to whether or not they received pravastatin after transplantation, and then compared with regard to transplant rejection, transplant coronary artery disease, and survival. RESULTS: Ninety-one patients received pravastatin after transplantation, whereas 37 did not receive any statins and served as controls. Pravastatin did not affect the overall incidence of rejections or number of rejection episodes. Hemodynamically significant rejection episodes occurred in 5 patients (5%) in the pravastatin group and 4 patients (11%) in the control group. Thus, pravastatin treatment apparently reduced the incidence of hemodynamically significant rejection episodes by 50% (p = 0.04). Transplant coronary artery disease (CAD) occurred in 10 patients (11%) in the pravastatin group and 9 patients (24%) in the control group. Treatment with pravastatin significantly reduced the incidence of transplant CAD (p = 0.05). Three- and 5-year survival rates in the pravastatin group were significantly better than in the control group (87% vs 68% and 82% vs 58%, respectively; p = 0.009). CONCLUSIONS: Pravastatin therapy offers long-term benefits to heart transplant recipients. It improves 5-year survival, lowers the risk of transplant CAD, and lowers the incidence of hemodynamically significant rejection episodes.

Adolescent↗
PubMed2005

Coronary artery disease alters ventricular repolarization dynamics in type 2 diabetes.

Ventricular repolarization dynamics (VRD) is an important predictor of outcome in diabetes. We examined the potential impact of coronary artery disease (CAD) on VRD in type 2 diabetic patients. We recorded 5-minute high-resolution resting electrocardiograms in 38 diabetic patients undergoing elective coronary angiography, and in 38 age- and gender-matched apparently healthy subjects (controls). Using leads-I and -II, time-domain indices of VRD were calculated. Coronary angiography was regarded as positive if >/= 50% stenosis was found. Angiography was positive in 21 diabetic patients (55%). Patients with CAD had a significantly higher degree of VRD than controls (SDNN(QT): 15.81 +/- 7.22 ms versus 8.94 +/- 6.04 ms; P < 0.001, rMSSD(QT): 21.02 +/- 7.07 ms versus 11.18 +/- 7.45 ms; P < 0.001). Ventricular repolarization dynamics in diabetic patients with negative angiograms did not differ from VRD in controls (SDNN(QT): 8.94 +/- 6.04 ms versus 7.44 +/- 5.72 ms; P = 0.67, rMSSD(QT): 11.18 +/- 7.45 ms versus 10.22 +/- 5.35 ms; P = 0.82). CAD increases VRD in patients with type 2 diabetes. Therefore, changes in ventricular repolarization in diabetic patients may be due to silent CAD rather than due to diabetes per se.

Case-Control Studies↗
PubMed2005

Pulmonary microthrombi during left ventricular assist device implantation.

Critically ill heart failure patients undergoing left ventricular assist device implantation have alterations in their coagulation profiles; as a result, hemorrhagic complications during the postoperative period are the most common and serious problems during device support of these patients. The use of aprotinin therapy is generally accepted for reducing bleeding after coronary artery bypass grafting procedures, heart transplantation, and insertion of a left ventricular assist device. We describe the case of a patient who had a suprasystemic increase in pulmonary artery pressure, caused by thromboembolic occlusion of the pulmonary arterioles after urgent implantation of a left ventricular assist device. The complications developed after the patient was weaned from cardiopulmonary bypass and heparinization was reversed with protamine. Although the thrombosis was successfully reversed with intraoperative administration of tissue plasminogen activator directly to the pulmonary artery, the patient died of massive hemorrhage 6 hours later. To our knowledge, the direct application of tissue plasminogen activator into the pulmonary artery in such a catastrophic situation has not been used elsewhere.

Blood Coagulation↗
PubMed2005

Orthotopic heart transplantation in a patient with D-transposition of the great arteries: after a Mustard procedure.

During heart transplantation, the atrial septum is most often used to reconstruct the right atrial reservoir. We report the case of a patient with corrected D-transposition of the great arteries who underwent successful cardiac transplantation despite the lack of an atrial septum. We then used the donor heart's atrial septum for the roof of the left atrium and used the recipient's left atrium for the back wall of the left atrium. The outcome was a more anatomically positioned transplanted heart, which avoided the duplication of the right and left atria that occurs in conventional orthotopic transplantation and that often leads to left-lower-lobe atelectasis and tricuspid regurgitation. This method of orthotopic transplantation should be considered for, but not limited to, the growing number of adults with congenital heart disease who require heart transplantation.

Adult↗
PubMed2004

Effects of a novel immune modulation therapy in patients with advanced chronic heart failure: results of a randomized, controlled, phase II trial.

OBJECTIVE: We sought to determine whether a novel, non-pharmacological form of immune modulation therapy (IMT), shown experimentally to reduce inflammatory and increase anti-inflammatory cytokines, improved outcomes in patients with advanced heart failure (HF). BACKGROUND: Immune activation contributes to the progression of HF, but treatments directed against inflammation have been largely unsuccessful. METHODS: Seventy-five HF patients (New York Heart Association [NYHA] functional class III to IV) were randomized to receive either IMT (n = 38) or placebo (n = 37) in a double-blind trial for six months, with continuation of standard HF therapy. Patients were evaluated using the 6-min walk test, changes in NYHA functional class, cardiac function, and quality of life assessments, as well as occurrence of death and hospitalization. RESULTS: There was no between-group difference in 6-min walk test, but 15 IMT patients (compared with 9 placebo) improved NYHA functional classification by at least one class (p = 0.140). The Kaplan-Meier survival analysis showed that IMT significantly reduced the risk of death (p = 0.022) and hospitalization (p = 0.008). Analysis of a clinical composite score demonstrated a significant between-group difference (p = 0.006). There was no difference in left ventricular ejection fraction, but there was a trend toward improved quality of life (p = 0.110). CONCLUSIONS: These preliminary findings are consistent with the hypothesis that immune activation is important in the pathogenesis of HF and establish the basis for a phase III trial to define the benefit of IMT in chronic HF.

Aged↗
PubMed2004

Arginine vasopressin levels are elevated and correlate with functional status in infants and children with congestive heart failure.

BACKGROUND: Arginine vasopressin (AVP) is a vasoactive hormone that acts on the kidney to conserve solute-free water and produces a potent vasoconstrictive effect during hypovolemic states. AVP levels are elevated in adults with congestive heart failure (CHF), and early clinical trials using AVP antagonists are being conducted. The purpose of this study was to determine if AVP levels (1) are elevated in children with CHF attributable to left ventricular dysfunction or pulmonary overcirculation attributable to large left-to-right shunts and (2) can predict functional clinical status. METHODS AND RESULTS: AVP levels were measured in patients with dilated cardiomyopathy (DCM) and CHF and in patients with large left-to-right intracardiac shunts. Each patient with DCM (ejection fraction percent <40%) was classified as NYHA functional class I through IV when the AVP level was drawn. Serum sodium was measured, serum osmolality was calculated, and echocardiograms and chest radiographs were performed on all study patients. AVP levels were also measured in age-matched controls. Mean AVP level in children with DCM (n=27) was 10.3 pg/mL (+/-12.8) versus 3.7 pg/mL (+/-2.4) in controls (n=15) (P<0.01). Mean AVP level in children with left-to-right shunts (n=14) was 13.9 pg/mL (+/-17.3) versus 3.5 pg/mL (+/-1.3) in controls (n=8) (P<0.04). In patients with DCM, AVP levels correlated directly with NYHA functional class (r2=0.73, P<0.001). CONCLUSIONS: Arginine vasopressin levels are elevated in infants and children with CHF attributable to left ventricular dysfunction and in infants with large left-to-right intracardiac shunts. Furthermore, there is a direct relationship between AVP level and the severity of heart failure in patients with DCM.

Arginine Vasopressin↗
PubMed2004

HeartMate vented-electric left ventricular assist system: technique for intrathoracic or intraperitoneal implantation via a left thoracotomy.

The HeartMate vented-electric left ventricular assist system (Thoratec Corp., Woburn, MA) has become widely accepted as a temporary bridge to transplantation. We describe a left thoracotomy technique in 3 patients for implanting this pump intrathoracically or intraperitoneally. In all 3 cases, long-term pump function was satisfactory. For HeartMate implantation, the left thoracotomy approach may be particularly useful when previous median sternotomies, coupled with the severe debilitation posed by chronic heart failure and hepatic dysfunction with resultant coagulopathy, would greatly increase the mortality and morbidity of a redo median sternotomy.

Cardiopulmonary Bypass↗