Biomedical subjects

Branislav Radovancevic

Publications and source records attributed to Branislav Radovancevic.

51 records · Page 3Linked to original sources

PubMed2003

Relations among heart failure severity, left ventricular loading conditions, and repolarization length in advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

In patients with heart failure (HF), low peak oxygen consumption (VO(2)) and prolonged QT interval or enhanced QT variability are associated with poor prognosis. Whether HF severity or left ventricular (LV) loading conditions can influence repolarization length is unknown. Survival, QTc interval, peak VO(2), clinical, laboratory, echocardiographic, and invasive hemodynamic data were analyzed in 154 transplant candidates; mortality was examined after a mean follow-up of 4.3 +/- 1.8 years. The relation between the QTc interval and other variables was examined using multivariate analysis and multiple correlation coefficients. Patients were stratified by peak VO(2) to study its relation with peak VO(2), mortality, loading conditions, and QTc intervals. Mean ejection fraction was 10 +/- 9%; mean cardiac index was 2.06 +/- 0.7 L/min/m(2). Seventy-one patients (47%) were dead at the end of study. Mortality and nonfatal ventricular arrythmias were higher (p <0.01) in patients with lower peak VO(2) and longer QTc intervals (p <0.001). An inverse correlation was found between QTc interval length and peak VO(2) (r = -0.790, p <0.0001). No correlation was found between QTc interval and LV loading conditions or the other analyzed variables. Thus, repolarization length measured by the QTc interval is inversely correlated with HF severity measured by peak VO(2) and is independent of LV loading conditions in patients with severe HF.

Cardiomyopathies↗

PubMed2003

Prolonged QTc interval and high B-type natriuretic peptide levels together predict mortality in patients with advanced heart failure.

BACKGROUND: The role of QTc interval prolongation in heart failure remains poorly defined. To better understand it, we analyzed the QTc interval duration in patients with heart failure with high B-type natriuretic peptide (BNP) levels and analyzed the combined prognostic impact of prolonged QTc and elevated BNP. METHODS AND RESULTS: QTc intervals were measured in 241 patients with heart failure who had BNP levels >400 pg/mL. QT interval duration was determined by averaging 3 consecutive beats through leads II and V4 on a standard 12-lead ECG and corrected by using the Bazett formula. QTc intervals were prolonged (>440 ms) in 122 (51%) patients and normal in 119 (49%). The BNP levels in these 2 groups were not significantly different (786+/-321 pg/mL in the prolonged QTc group versus 733+/-274 pg/mL in the normal QTc group, P=0.13). During 6 months of follow-up, 46 patients died, 9 underwent transplantation, and 17 underwent left ventricular assist device implantation. The deaths were attributed to pump failure (n=24, 52%), sudden cardiac death (n=18, 39%), or noncardiac causes (n=4, 9%). Kaplan-Meier survival rates were 3 times higher in the normal QTc group than in the prolonged QTc group (P<0.0001). On multivariate analysis, prolonged QTc interval was an independent predictor of all-cause death (P=0.0001), cardiac death (P=0.0001), sudden cardiac death (P=0.004), and pump failure death (P=0.0006). CONCLUSIONS: Prolonged QTc interval is a strong, independent predictor of adverse outcome in patients with heart failure with BNP levels >400 pg/mL.

Aged↗

PubMed2003

Continuous axial-flow left ventricular assist device (Jarvik 2000) maintains kidney and liver perfusion for up to 6 months.

BACKGROUND: The Jarvik 2000 axial flow left ventricular assist device (LVAD), under development for the past decade, has the potential to support patients temporarily until cardiac transplantation or as a permanent circulatory support, without the size limitations of other implantable systems. METHODS: To assess its ability to perfuse the kidneys and liver, we monitored renal and hepatic function in 10 patients who received the Jarvik 2000 LVAD as a bridge to transplantation. Left ventricular assistance was maintained for up to 214 days (> 6 months), and renal and hepatic function were monitored at least weekly. RESULTS: Renal function before LVAD implantation in these patients was normal in 7 (creatinine, < 1.5) and moderately impaired in 3 (creatinine, 1.2 to 2.0). Hepatic function was normal in 7 patients before LVAD implantation (total bilirubin< 1.2; serum glutamic-oxaloacetic transaminase (SGOT), < 40; serum glutamic-pyruvic transaminase (SGPT), < 50) and normal at the time of transplantation in all 10 patients. Of the 3 patients with abnormal hepatic function before LVAD implantation, 1 patient had also had moderate renal dysfunction. CONCLUSIONS: Despite reduced pulsatility, the Jarvik 2000 LVAD improves or maintains excellent renal and hepatic function during periods of circulatory assistance in patients awaiting transplantation.

Adult↗

PubMed2003

Outcomes in patients with low left ventricular ejection fraction after heart transplantation.

OBJECTIVES: Low left ventricular ejection fraction (EF) after heart transplantation (HT) is considered an ominous sign. We reviewed our database in order to determine outcomes in patients with low EF after HT and to identify a subset of patients who would benefit from immediate retransplantation. METHODS: We identified 825 patients who underwent HT at our institution between December 1983 and July 1999. Of these, 81 patients (70 men, 11 women; age, 48+/-12 years) had low (<35%) EF as determined by radionuclide ventriculography. Post-transplantation survival; duration of low-EF episodes (>2 years vs. <2 years); and incidence of transplant rejection, infection, and transplant coronary artery disease (CAD) were determined for these patients. RESULTS: On average, low EF developed 800+/-1029 days after HT and lasted 550+/-756 days until improvement, repeat HT, or death of the patient. Actuarial survival was 79% at 1 year, 55% at 3 years, and 46% at 5 years. Shorter (<2-year) episodes of low EF tended to have an earlier onset than prolonged (>2-year) episodes (656 days vs. 1341 days) (P=0.014). Patients with prolonged episodes (n=17) survived longer than patients with shorter episodes (n=64) (2247 days vs. 1266 days) (P=0.002). The incidence of hemodynamically significant rejection was lower in the prolonged low-EF group (6% [1/17] vs. 26% [17/64]) (P=0.03). The incidence of infection (31% vs. 53%) and incidence of transplant CAD (47% vs. 39%) did not differ significantly between the prolonged and shorter low-EF groups. CONCLUSIONS: Low EF after HT, especially with later onset, is not associated with poor survival and is not related to hemodynamically significant rejection. These data further indicate that the presence of low EF even in the setting of CAD is not by itself an indication for repeat HT.

Adult↗

PubMed2003

Retransplantation in 7,290 primary transplant patients: a 10-year multi-institutional study.

BACKGROUND: Cardiac retransplantation is a controversial procedure due to the disparity between donor heart demand and supply. METHODS: Of 7,290 patients undergoing primary cardiac transplantation between January 1990 and December 1999 at 42 institutions contributing to the Cardiac Transplant Research Database (CTRD), 106 patients later underwent a second and 1 patient a third cardiac transplant procedure. RESULTS: The actuarial freedom from retransplantation was 99.2% and 96.8% at 1 and 10 years, respectively. Reasons for retransplantation included early graft failure (n = 34), acute cardiac rejection (n = 15), coronary allograft vasculopathy (CAV, n = 39), non-specific graft failure (n = 7), and miscellaneous (n = 10). The only risk factor associated with retransplantation was younger age, reflecting the policy of preferential retransplantation of younger patients. Survival after retransplantation was inferior to that after primary transplantation (56% and 38% at 1 and 5 years, respectively). Risk factors associated with death after retransplantation included retransplantation for acute rejection (p = 0.0005), retransplantation for early graft failure (p = 0.03), and use of a female donor (p = 0.005). Survival after retransplantation for acute rejection was poorest (32% and 8% at 1 and 5 years, respectively) followed by retransplantation for early graft failure (50% and 39% at 1 and 5 years, respectively). Survival after retransplantation for CAV has steadily improved with successive eras. CONCLUSIONS: The results of retransplantation for acute rejection and early graft failure are poor enough to suggest that this option is not advisable. However, retransplantation for CAV is currently associated with satisfactory survival and should continue to be offered to selected patients.

Actuarial Analysis↗

PubMed2003

Left ventricular assist devices: an alternative to medical therapy for end-stage heart failure.

Although aggressive medical therapy and ultimately cardiac transplantation have long been the therapeutic mainstays for patients with end-stage heart failure, the left ventricular assist device (LVAD), which was originally used clinically as a bridge to transplantation, may also be used as destination therapy. LVAD therapy for selected patients has been shown in the REMATCH trial to be superior to medical therapy in ameliorating symptoms and improving outcome in patients with terminal heart failure. LVAD therapy has also proved useful in improving native heart function by neuroendocrine modulation and reverse remodeling. Furthermore, current evidence suggests that when LVAD therapy is utilized to improve ventricular function, it may be further enhanced when combined with aggressive medical therapy.

Clinical Trials as Topic↗

PubMed2003

Ex vivo resuscitation of adult pig hearts.

One possible way to expand the human heart donor pool is to include non-heart-beating human donors. To begin validating this approach, we developed an ex vivo cardiac perfusion circuit to support large mammalian hearts in Langendorff mode and beating-ejecting mode and to assess and improve their ischemic tolerance. In vivo hemodynamic data and heparinized blood (4.0 +/- 0.5 L) were collected from 6 anesthetized pigs. Hearts were isolated and connected to a recirculating perfusion circuit primed with autologous buffered blood (pH, 7.40). After retrograde aortic perfusion in Langendorff mode, the left atrium was gravity-filled at 10-20 mmHg, and the left ventricle began to eject against a compliance chamber in series with a systemic reservoir set to a hydraulic afterload of 100-120 mmHg. Left ventricular function was restored and maintained in all 6 hearts for 30 min. Cardiac output, myocardial oxygen consumption, stroke work, aortic pressure, left atrial pressure, and heart rate were measured. The mean myocardial oxygen consumption was 4.8 +/- 2.7 mL/min/100 g (95.8% of in vivo value); and mean stroke work, 5.3 +/- 1.1 g x m/100 g (58.95% of in vivo value). One resuscitated heart was exposed to 30 min of normothermic ischemic arrest, then flushed with Celsior and re-resuscitated. The ex vivo perfusion method described herein restored left ventricular ejection function and allowed assessment of ischemic tolerance in large mammalian hearts, potentially a 1st step toward including non-heart-beating human donors in the human donor pool.

Animals↗

PubMed2002

Use of autologous auricular chondrocytes for lining artificial surfaces: a feasibility study.

BACKGROUND: Auricular elastic cartilage is a potential source of autologous cells for lining the luminal surfaces of cardiovascular prostheses. We tested this potential in vitro and in vivo using a left ventricular assist device (LVAD) and a calf model. METHODS: In vitro, auricular cartilage was harvested from the anesthetized ear of a calf, isolated, and cultured on tissue culture dishes. Primary chondrocytes were typed by immunocytochemistry, transferred into culture media, passaged twice, and seeded onto the blood-contacting luminal surfaces of four LVADs (HeartMate; Thoratec Corporation, Woburn, MA). Seeded cell linings were preconditioned under simulated flow conditions to promote cell adhesion to luminal surfaces. Seeding efficiency and cumulative cell loss under flow conditions were quantitated. In vivo, one of the four autologous chondrocyte-lined and preconditioned LVADs was implanted into the tissue-donor calf; run for 7 days; explanted; and evaluated grossly, by scanning electron microscopy, and by transmission electron microscopy. RESULTS: The efficiency of seeding chondrocytes onto the luminal surfaces of the four LVADs was 95.11% +/- 4.23% (n = 4). Cumulative cell loss during preconditioning under flow conditions in vitro did not exceed 12% (n = 4). After 7 days of in vivo implantation, the luminal surfaces of the implanted LVAD demonstrated an intact, strongly adherent cellular lining. CONCLUSIONS: Auricular elastic cartilage is a ready and easily accessible source of chondrocytes whose ability to produce collagen II and other important extracellular matrix constituents allows them to adhere strongly to the luminal surfaces of LVADs. The simple method of isolating and expanding auricular chondrocytes presented here could be used to provide strongly adherent autologous cell linings for LVADs and other cardiovascular devices. If and when chondrocytes can be genetically engineered to produce antithrombogenic factors and then used to line the luminal surfaces of LVADs or other cardiovascular prostheses, they may be able to improve the hemocompatibility of the blood-biomaterial interface in such devices. Our successful feasibility study in a calf model warrants further studies of this concept in vivo.

Animals↗

PubMedDate not supplied

Biventricular support with the Jarvik 2000 axial flow pump: a feasibility study.

Patients with congestive heart failure who are supported with a left ventricular assist device (LVAD) may experience right ventricular dysfunction or failure that requires support with a right ventricular assist device (RVAD). To determine the feasibility of using a clinically available axial flow ventricular assist device as an RVAD, we implanted Jarvik 2000 pumps in the left ventricle and right atrium of two Corriente crossbred calves (approximately 100 kg each) by way of a left thoracotomy and then analyzed the hemodynamic effects in the mechanically fibrillated heart at various LVAD and RVAD speeds. Right atrial implantation of the device required no modification of either the device or the surgical technique used for left ventricular implantation. Satisfactory biventricular support was achieved during fibrillation as evidenced by an increase in mean aortic pressure from 34 mm Hg with the pumps off to 78 mm Hg with the pumps generating a flow rate of 4.8 L/min. These results indicate that the Jarvik 2000 pump, which can provide chronic circulatory support and can be powered by external batteries, is a feasible option for right ventricular support after LVAD implantation and is capable of completely supporting the circulation in patients with global heart failure.

Animals↗

PubMedDate not supplied

Prolonged controlled hemorrhagic shock in a swine model: is there a role for mechanical circulatory assistance?

Outcomes of mechanical circulatory assistance during hemorrhagic shock were evaluated in a swine model. Pigs were bled to a mean arterial pressure of 35 mm Hg (group I, n = 3) or 40 mm Hg (group II, n = 5; group III, n = 5), maintained there for 30 minutes, and then resuscitated with fluids alone (groups I and II) or fluids plus mechanical circulatory assistance (group III). Mean blood loss was greater in group I than in groups II or III (1,037 +/- 212 vs. 862 +/- 387 ml vs. 681 +/- 117 ml, respectively; I vs. III, p < 0.05) and survival was shorter (230 +/- 25.5 min vs. 709 +/- 251 min vs. 662 +/- 428 min, respectively; I vs. II or III, p < 0.05). Cardiac arrhythmia caused death in most cases. Mean biochemical parameters increased progressively in all cases. Left anterior descending coronary artery flow stayed relatively constant in group II but increased in group III. Superior mesenteric artery flow returned to baseline in group II but increased in group III. Cardiac output was similar in groups II and III, but SGOT levels significantly differed (750 +/- 135 U/L vs. 359 +/- 157 U/L; p < 0.005). These results suggest that the swine model will be useful for studying ways to improve outcomes after prolonged hemorrhagic shock.

Animals↗

PubMedDate not supplied

Biventricular support with the Jarvik 2000 ventricular assist device in a calf model of pulmonary hypertension.

The Jarvik 2000 ventricular assist device (VAD) is clinically efficacious for treating end-stage left ventricular failure. Because simultaneous right ventricular support is also occasionally necessary, we developed a biventricular Jarvik 2000 technique and tested it in a calf model. One VAD was implanted in the left ventricle with outflow-graft anastomosis to the descending aorta. The other VAD was implanted in the right ventricle with outflow-graft anastomosis to the pulmonary artery. Throughout the 30 day study, hemodynamic values were continuously monitored. On day 30, both pumps were evaluated at different speeds, under various hemodynamic conditions. By gradually occluding the pulmonary artery proximally or distally, we simulated varying degrees of high pulmonary vascular resistance, right ventricular hypertension, global heart failure, or ventricular fibrillation. The two VADs maintained biventricular support even during pulmonary artery occlusion and ventricular fibrillation, yielding a cardiac output of 3-11 L/min, left ventricular end-diastolic pressure of 11-24 mm Hg, and central venous pressure of 9-25 mm Hg. End-organ function was unimpaired, and no major adverse events occurred. The dual VADs offered safe, effective biventricular assistance in the calf. Additional studies are needed to assess the effects of lowered pulse pressure upon the pulmonary circulation and to develop a single pump speed controller.

Animals↗

PubMedDate not supplied

Evaluation of a new cardiac recovery system in a bovine model of volume overload heart failure.

We evaluated the short-term hemodynamic efficacy of the Cancion cardiac recovery system (CRS) in a bovine model of volume overload heart failure. We created severe mitral regurgitation (MR) by disrupting the mitral chordae tendineae of two calves, which were allowed to survive for 13 and 11 months. Four hours before we killed the calves, we introduced the CRS, which maintained flows of 1.2 L/min. Hemodynamic data were recorded before and after MR creation and CRS initiation. Left ventriculography was performed at those same intervals and 4 hours after CRS initiation. After chordal disruption, the left ventricular end-diastolic pressure (LVEDP) increased from 14 to 23 mm Hg in calf 1 and 15 to 27 mm Hg in calf 2. After 4 hours of CRS support, the LVEDP decreased from 23 to 8 mm Hg (calf 1) and 27 to 14 mm Hg (calf 2); dP/dt increased from 1,373 to 2,900 mm Hg/s (calf 1) and 1,068 to 2,384 mm Hg/s (calf 2). MR decreased from 3+ to 1 in calf 2 but could not be determined in calf 1. In this bovine model of volume overload heart failure, the CRS unloaded the left ventricle and reduced the afterload. Future trials will determine the pump's ability to treat congestive heart failure.

Animals↗

PubMedDate not supplied

Vascular thrombosis during support with continuous flow ventricular assist devices: correlation with computerized flow simulations.

Continuous flow pumps are increasingly used to treat severe heart failure. These pumps alter flow physiology by lowering pulsatility in the arterial circulation. In patients with peripheral stenosis, continuous flow pumps may lead to thrombosis of peripheral vessels, possibly predisposing to vascular thrombosis in areas of non-flow-limiting stenosis. The authors performed a computerized flow modeling simulation to analyze the effects of altered hemodynamics in a stenotic area. Drawing on previous clinical experience, we modeled a stenotic area in the common carotid artery. Computerized flow modeling revealed blood stagnation zones with low shear stress and velocity adjacent to the stenotic area during nonpulsatile flow. Such stagnation was not present during pulsatile flow. These results indicate a mechanism by which altered physiologic flow may accelerate occlusion of arterial conduits in patients with preexisting stenosis. This finding may be important for patients with continuous flow devices who have peripheral vascular disease; therefore, further study is warranted.

Blood Flow Velocity↗

PubMedDate not supplied

Brain natriuretic peptide levels and response to cardiac resynchronization therapy in heart failure patients.

The authors used brain natriuretic peptide (BNP) as a reliable marker to identify nonresponders to cardiac resynchronization therapy (CRT) in patients with advanced heart failure. The study included 70 patients with left ventricular dysfunction (mean ejection fraction, 21+/-4%) and left bundle branch block (QRS duration, 164+/-25 milliseconds) treated with CRT. The authors reviewed data on New York Heart Association functional class, baseline ejection fraction, sodium, creatinine, QRS duration, and BNP levels 3 months before and after CRT therapy. The authors compared results of 42 patients who survived (973+/-192 days) after CRT implantation (responders) to those of 28 patients (nonresponders) who either expired (n=21) or underwent heart transplantation (n=5) or left ventricular assist device implantation (n=2) after an average of 371+/-220 days. Mean BNP levels after 3 months of CRT decreased in responders from 758+/-611 pg/mL to 479+/-451 pg/mL (P=.044), while in nonresponders there was increase in BNP levels from 1191+/-466 pg/mL to 1611+/-1583; P=.046. A rise in BNP levels was associated with poor response (death or need for transplantation or left ventricular assist device and impaired long-term outcome), which makes it a good predictor to identify such patients.

Aged↗

PubMedDate not supplied

The effect of administering erythropoiesis-stimulating proteins in patients with chronic heart failure: results from a retrospective study.

Anemia is prevalent in patients with chronic heart failure and is associated with worse symptoms and poor prognosis. The authors reviewed the charts of all patients (N=467) treated at Texas Heart Institute from January 2000 to October 2003, during which time a clinical protocol offered treatment with erythropoiesis-stimulating proteins. Post-treatment, the authors observed a significant increase in mean +/- SD hemoglobin, from 9.9+/-1.1 g/dL to 11.7+/-1.5 g/dL (P<.0001), improvement of renal function (a decrease in mean levels of creatinine and blood urea nitrogen), and fewer hospital admissions (1.0+/-1.4 vs 1.8+/-1.6; P=.0003) without an increase in adverse clinical events, compared with pretreatment and compared with an untreated control group. These results suggest a potential benefit of anemia treatment with recombinant erythropoiesis-stimulating proteins in patients with chronic heart failure.

Aged↗