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Biomedical subjects

Joseph G Rogers

Publications and source records attributed to Joseph G Rogers.

At least 19 recordsLinked to original sources

Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure.

BACKGROUND: Treatment of decompensated heart failure often includes the use of intravenous vasoactive medications, but the effect on outcome has not been clearly defined. METHODS: Data from 433 patients enrolled in the ESCAPE trial were analyzed to determine 6-month risks of all-cause mortality and all-cause mortality plus rehospitalization associated with the use of vasodilators, inotropes, and their combination. Patients had a mean left ventricular ejection fraction of 19%, 6-minute walk distance of 414 ft, and systolic blood pressure of 106 mm Hg. The main outcome measure was multivariable risk-adjusted 6-month hazard ratios (HRs). RESULTS: Overall 6-month mortality was 19%. Risk-adjusted HRs were not statistically significant for vasodilators (1.39, 95% CI 0.64-3.00), but were significant for inotropes (2.14, 95% CI 1.10-4.15) and the combination (4.81, 95% CI 2.34-9.90). Risk-adjusted 6-month mortality plus rehospitalization HRs were not significant for vasodilators (1.20, 95% CI 0.81-1.78, P = .37), but were significant for inotropes (1.96, 95% CI 1.37-2.82, P < .001) and their combination (2.90, 95% CI 1.88-4.48, P = .001). The decision to use vasodilators or inotropes was determined by hemodynamic parameters and renal function, but the main factor was treatment site. CONCLUSIONS: In ESCAPE, the choice of medications was mainly determined by the treatment site. Use of inotropic agents was associated with adverse outcomes, whereas the use of vasodilators was not. Inotropes in combination with vasodilators identified a group with the highest mortality. Prospective studies are needed to establish the appropriate use of vasoactive medications in this population.

Adult↗

Marginal cardiac allografts do not have increased primary graft dysfunction in alternate list transplantation.

BACKGROUND: Clinical success with modern heart transplantation (HT) has led to the development of an alternate list (AL) HT strategy, matching marginal cardiac allografts with recipients who do not meet standard criteria for HT. Marginal allografts may be at an increased risk for primary graft dysfunction (PGD), the leading cause of early mortality after HT.(1) The incidence of PGD in AL HT relative to standard list (SL) HT has not been evaluated, and may contribute to the greater mortality associated with AL HT.(2) The objective of this study was to determine the incidence of and predictors for PGD. METHODS AND RESULTS: A retrospective analysis was performed on 260 consecutive adult patients undergoing either SL HT (n=207) or AL HT (n=53) at our institution from 1/2000 to 1/2005. PGD was defined by requirement for mechanical circulatory support immediately post-HT or more broadly as the need for either mechanical support or high-dose inotrope (epinephrine > or = 0.07 microg/kg/min). Donor hearts allocated to AL recipients were turned down for SL HT for reasons that included coronary disease, left ventricular dysfunction or hypertrophy, and high-dose inotropic requirement. AL HT recipients were significantly older, with a higher proportion of diabetes mellitus and ischemic cardiomyopathy. Both groups experienced a similar incidence of significant rejection, but overall mortality was higher in the AL HT group. (2) The incidence of PGD did not differ between AL and SL HT recipients. Pre-transplant VAD and prolonged total ischemic times (> or = 4.5 hours) were independent predictors of PGD. CONCLUSIONS: Select marginal donor hearts used in AL HT do not have an increased incidence of PGD. Pre-transplant VAD and prolonged ischemic times are more important determinants of PGD. These data support continued aggressive utilization of marginal donor hearts in AL HT.

Adult↗

Cardiac transplantation following ACORN CorCap device implantation.

Passive ventricular restraint devices, such as the ACORN CorCap, have been introduced as a potential therapy for congestive heart failure (CHF). These mesh devices act as a mechanical support for the dilated heart. Due to incorporation of the device to the epicardium, concerns about the feasibility of reoperation following CorCap placement have been raised. This case illustrates that although technically challenging, reoperation for heart transplantation after CorCap implantation is feasible and safe.

Adult↗

Same bridge, new destinations rethinking paradigms for mechanical cardiac support in heart failure.

Mechanical cardiac support with ventricular assist devices is an established therapy for a variety of clinical scenarios, including postcardiotomy shock, "bridge to transplant," and "destination therapy." At present, device development, clinical trial design, regulatory approval, and reimbursement decisions for the clinical application of mechanical cardiac support devices continue to be considered in the context of these clinical indications. Although understandable from a historical perspective, these arbitrary divisions are inconsistent with the clinical realities of advanced heart failure therapy. By narrowly focusing on transplant eligibility at a static point in the clinical course, current guidelines impede the broader application of ventricular assist device technology to the growing population of patients who may benefit from this therapy.

Heart Failure↗

Relationship between renal function and left ventricular assist device use.

BACKGROUND: Poor renal function may affect outcomes after left ventricular assist device (LVAD) placement. Conversely, LVADs may optimize circulation and improve renal function. METHODS: To assess the relationship between renal function and LVAD use, changes in creatinine clearances (CrCl, in mL/min) were assessed retrospectively in 220 patients who underwent LVAD placement. These patients were also divided into four groups based on CrCl quartiles (< 47, 48-68, 69-95, and > 95) and compared for outcomes post-LVAD placement. RESULTS: Eighty-four patients died on LVAD support. Survival on LVAD was worse for patients with the worst baseline CrCl (42%, 52%, 63%, and 79% for 6 month and 26%, 34%, 47%, and 66% for 12 month survival for quartiles 1-4; both p < 0.01 for trend). Adjusting for other covariates, patients in the lowest CrCl quartile were at a higher risk of dying postimplant (odds ratio 1.95, 95% confidence interval 1.14-3.63). Paired sample analysis showed the following changes in CrCl: preoperative to week 1, 77.0 +/- 46.6 to 92.1 +/- 51.1 (p < 0.01; n = 202), week 1 to 2, 89.4 +/- 49.2 to 95.2 +/- 52.4 (p = 0.01, n = 171), week 2 to 3, 107.5 +/- 58.1 to 113.7 +/- 66.1 (p = 0.16, n = 74), and week 3 to 4, 111.1 +/- 56.6 to 110.5 +/- 56.8 (p = 0.87, n = 60). For the 60 patients with baseline CrCl less than 50, CrCl increased from 36.7 +/- 9.2 to 60.1 +/- 35.5 (p < 0.01; n = 55 pairs) from preimplant to week 1. In 37 of these patients (62%) on intraaortic balloon pump support preimplant, CrCl increased from 38.4 +/- 8.2 to 67.9 +/- 40.3 mL/minute (p < 0.01) during week 1 postimplant. Recovery of renal function to CrCl greater than 50 was associated with a trend towards better 30-day survival (84% vs 66%, p = 0.09). CONCLUSIONS: Baseline poor renal function is associated with worse outcomes after LVAD implantation. However, renal function improves substantially and rapidly in post-LVAD survivors and is associated with improved outcomes. These data underscore the importance of careful patient selection for LVAD therapy.

Adult↗

Randomized trial of a nurse-administered, telephone-based disease management program for patients with heart failure.

BACKGROUND: Heart failure is a common and important cause of morbidity and mortality. Disease management offers promise in reducing the need for hospitalization and improving quality of life for heart failure patients, but experimental data on the efficacy of such programs are limited. METHODS AND RESULTS: A total of 151 patients hospitalized with heart failure were randomized to usual care or scheduled telephone calls by specially trained nurses promoting self-management and guideline-based therapy as prescribed by primary physicians. Nurses also screened patients for heart failure exacerbations, which they managed with supplemental diuretics or by contacting the primary physician for instructions. Outcomes included time to hospital encounter, mortality, number and cost of hospitalizations, functional status, and satisfaction with care. Intervention patients had a longer time to encounter (hazard ratio [HR] = 0.67; 95% confidence interval [CI] 0.47-0.96; P = .029), hospital readmission (HR = 0.67; CI 0.46-0.99; P = .045), and heart failure-specific readmission (HR = 0.62; CI 0.38-1.03; P = .063). The number of admissions, hospital days, and hospital costs were significantly lower during the first 6 months after intervention but not at 1 year. The intervention had little effect on functional status, mortality, and satisfaction with care. CONCLUSION: A nurse-administered, telephone-based disease management program delayed subsequent health care encounters, but had minimal impact on other outcomes.

Aged↗

Different roles for matrix metalloproteinase-2 and matrix metalloproteinase-9 in the pathogenesis of cardiac allograft rejection.

Recent studies have shown an increased expression of several matrix metalloproteinases (MMP) during cardiac, renal and pulmonary allograft rejection. To further define the roles of MMP-2 and MMP-9 in the pathogenesis of cardiac allograft rejection, BALB/c cardiac allografts were transplanted into MMP-2-deficient (-/-) and MMP-9-/- mice. Allografts rejected by wild-type mice revealed a significant increase in MMP-2 and MMP-9 expression. MMP-2-deficiency significantly prolonged allograft survival time. Functioning allografts harvested from MMP-2-/- mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-2+/+ mice at the same time. In contrast, MMP-9-deficiency significantly decreased allograft survival time. Functioning allografts harvested from MMP-9+/+ mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-9-/- mice at the same time. MMP-2-/- recipients showed decreased T-cell alloreactivity mediated by a defect in dendritic cell stimulatory and T-cell responsive capacities. In contrast, MMP-9-/- recipients showed increased T-cell alloreactivity mediated by a significant increased in dendritic cell stimulatory and T-cell responsive capacities. These results indicate that MMP2 and MMP-9 play significantly different roles in the process of cardiac allograft rejection.

Animals↗

Survival of patients removed from the heart transplant waiting list.

OBJECTIVE: End-stage heart failure has been associated with high mortality in the absence of transplantation. We evaluated the outcome of patients receiving optimal medical therapy who were removed from the cardiac transplant waiting list to determine survival and predictors of mortality. METHODS: We performed a retrospective review of 27 patients removed from the cardiac transplant waiting list from 1999 to 2001 at our institution. RESULTS: Mean age was 53 +/- 11 years; 16 of the patients were male. Status was IB in 3 cases and II in 24. Median time on the list was 32 months, and median follow-up was 2.9 years. Patients were removed from the transplant list because of either clinical improvement (group A, n = 18) or deterioration (group B, n = 9). In group A, 13 patients had improved functional status and 10 were in New York Heart Association class 1 or 2; 16 had improved echocardiographic left ventricular function. Survivals at 3 years were 100% in group A and 44% in group B (P <.01). CONCLUSION: Patients with end-stage heart failure who have clinical response to medical therapy have excellent 3-year survival. These data suggest the necessity of close evaluation of patients waiting for transplantation, with a low threshold for inactivation if persistent clinical improvement is observed.

Cause of Death↗

Cardiac transplantation at Duke University Medical Center.

Since beginning cardiac transplantation in 1985, Duke University Medical Center has performed 485 de novo heart transplants in adult recipients. Our program has broadened the access of patients to transplantation through the aggressive use of ventricular assist devices as bridge to transplant in patients with acute heart failure and shock, as well as through the introduction of an alternate list program for suboptimal transplant candidates. Despite this broadening of the recipient pool, our long-term outcomes have remained good, with 5-year survival of 75% and 10-year survival of 51%. Continued advances in immunosuppression and treatment for cardiac allograft vasculopathy seem likely to continue to improve long-term outcomes from cardiac transplantation. Expanding indications for VAD support (such as destination therapy) and continued improvements in this technology seem certain to impact patient selection and therefore the results of transplantation in the future. Appropriate triage of patients with advanced heart failure among available therapies will be the cornerstone of optimizing outcomes in this critically ill patient population.

Academic Medical Centers↗

The effect of beta-adrenergic blockers on the prognostic value of peak exercise oxygen uptake in patients with heart failure.

OBJECTIVES: Our aim was to determine the effect of beta-adrenergic blockade on the prognostic value of peak oxygen consumption testing in patients with heart failure. BACKGROUND: Peak oxygen consumption has been shown to be a useful prognostic tool in patients with heart failure. However, studies demonstrating the utility of peak oxygen consumption were conducted before beta-blocker therapy became widespread. Thus, our objective was to determine the effect of beta-blockers on the prognostic value of peak oxygen consumption in patients with heart failure. METHODS: Actuarial, anthropomorphic, hemodynamic and exercise ventilatory data were collected from 369 patients with heart failure. Death and orthotopic heart transplants were the events tracked. Patients were divided into those taking beta-blockers and those not taking them. Event-free survival days were calculated. RESULTS: One hundred ninety-nine patients on beta-blockers and 170 not on beta-blockers were studied. There were 40 orthotopic heart transplants and 82 deaths during follow-up. Peak oxygen consumption (milliliters per kilogram per minute) trended toward being an independent predictor of event-free survival (p = 0.055). In patients on and not on beta-blockers, a peak oxygen consumption of >14 ml/kg.min was associated with a 1-year event rate of approximately half of that associated with a peak oxygen consumption </=14 ml/kg x min. However, for every level of peak oxygen consumption, the event rate was lower in the group taking beta-blockers. CONCLUSIONS: Beta-blocker status does not change the predictive power of peak oxygen consumption in patients with heart failure, but beta-blocker status is important to consider when using peak oxygen consumption to predict event-free survival in patients with heart failure.

Adrenergic beta-Antagonists↗

Timing of cardiac transplantation in patients with heart failure receiving beta-adrenergic blockers.

BACKGROUND: Previous work shows that patients with heart failure patients who have peak oxygen consumption (VO2 peak) >14 ml/kg/min do not derive a survival benefit from cardiac transplantation. However, this was shown before beta-blocker therapy for patients with systolic heart failure became common, and beta-blockers improve survival in patients with heart failure without changing VO(2) peak. Our purpose was to re-evaluate the utility of VO(2) peak >14 ml/kg/min as an indicator of the need for cardiac transplantation in patients with heart failure who are taking beta-blockers. METHODS: Actuarial, hemodynamic, and exercise ventilatory data were collected from 540 patients with heart failure, 256 of whom were taking beta-blockers. We tracked death and cardiac transplantation. We stratified the percentage of patients event-free 1 and 3 years after VO(2) peak study by their VO(2) peak and beta-blocker status, and compared 1- and 3-year post-transplant survival (United Network of Organ Sharing [UNOS] data). We also compared total mortality for the patients with heart failure as stratified by beta-blocker stats and VO(2) peak (excluding the 42 who underwent transplantation) with UNOS post-transplant survival. RESULTS: Patients with heart failure who were receiving beta-blockers and whose VO(2) peak was > or =12 ml/kg/min had greater 1- and 3-year event-free survival rates (95% confidence intervals, 92.6%-96.6% and 85.8%-96.0%) than did post-transplant patients (83.9%-86.3% and 75.4%-76.6%). However, in patients with heart failure not taking beta-blockers, VO(2) peak <14 ml/kg/min was associated with worse 3-year survival (38.9 - 62.1%) than that for post-transplant patients. Excluding the 42 patients with heart failure in our study who underwent transplantation and then evaluating survival of the remaining patients with heart failure (not event-free survival) did not substantially change these results. CONCLUSIONS: Patients with heart failure who are receiving beta-blockers do not derive a survival advantage at 1 and 3 years after cardiac transplantation if VO(2) peak is > or =12 ml/kg/min. Patients not taking beta-blockers whose VO(2) peak is <14 ml/kg/min have superior survival with cardiac transplantation.

Adrenergic beta-Antagonists↗

Up-regulation of connexin45 in heart failure.

INTRODUCTION: Heart failure is associated with reduced expression of the major gap junction protein connexin43 (Cx43), which may contribute to arrhythmias and sudden cardiac death in this patient population. Other cardiac connexins may be altered as well. Because connexin45 (Cx45) has been shown to colocalize with Cx43, we determined whether the number, size, or distribution of Cx45 gap junctions is altered in the failing heart. METHODS AND RESULTS: Cx45 expression levels were measured by immunoblotting and quantitative immunostaining in failing and control human left ventricles. Total Cx45 protein was significantly (P = 0.021) up-regulated 1.8-fold in failing hearts. Cx45 immunohistochemical signal was increased by 80% (P = 0.005) due to a 3.5-fold increase in the number of gap junctions containing Cx45. Cx45 mRNA was not altered in failing hearts, suggesting reduced degradation of Cx45 protein in the failing heart. Cx43 signal, on the other hand, was reduced by 49% in failing hearts. Double-label experiments demonstrated colocalization of Cx45 and Cx43 in the same gap junctions. CONCLUSION: Cx45 is markedly enhanced in the failing heart. Up-regulation of Cx45 in conjunction with down-regulation of Cx43 could result in abnormal impulse propagation and generation of ventricular arrhythmias, thereby predisposing patients in heart failure to sudden cardiac death.

Adult↗

Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine whether patients with idiopathic dilated cardiomyopathy (IDCM) exhibit alterations in myocardial fatty acid and glucose metabolism. BACKGROUND: Alterations in myocardial metabolism have been implicated in the pathogenesis of heart failure (HF); however, studies of myocardial metabolic function in human HF have yielded conflicting results. Animal models of HF have shown a downregulation of the expression of enzymes of fatty acid beta-oxidation that recapitulates the fetal energy metabolic program, in which fatty acid metabolism is decreased and glucose metabolism is increased. METHODS: Seven patients with IDCM (mean left ventricular ejection fraction 27 +/- 8%) and 12 normal controls underwent positron emission tomography for measurements of myocardial blood flow (MBF), myocardial oxygen consumption (MVO(2)), myocardial glucose utilization (MGU), myocardial fatty acid utilization (MFAU) and myocardial fatty acid oxidation (MFAO). RESULTS: The systolic and diastolic blood pressures, plasma substrates and insulin levels, MBF and MVO(2), were similar between groups. The rates of MFAU and MFAO were significantly lower in IDCM than in the normal control group (MFAU: 134 +/- 44 vs. 213 +/- 49 nmol/g/min, p = 0.003; and MFAO: 113 +/- 50 vs. 205 +/- 49 nmol/g/min, p = 0.001) and the rates of MGU were significantly higher in IDCM than the normal control group (MGU: 247 +/- 63 vs. 125 +/- 64 nmol/g/min, p < 0.001). CONCLUSIONS: Patients with IDCM exhibit alterations in myocardial metabolism characterized by decreased fatty acid metabolism and increased myocardial glucose metabolism, a pattern similar to that shown in animal models of HF. Whether alterations in myocardial metabolism constitute an adaptive response or mediate the development of HF remains to be determined.

Adult↗

Surgical management of Novacor drive-line exit site infections.

Implantable left ventricular assist device (LVAD) drive-line exit site infection, an expected consequence of currently available device use, continues to be a significant limiting factor in long-term support. We theorize that the mechanism behind the establishment of the most chronic exit site infections involves a shearing torsion injury that disrupts the tissue adherence interface with the drive-line. The resulting neo-epithelialized drainage tract prevents permanent clearance of the infection with antibiotics alone. The proposed treatment strategy of established infections involves aggressive surgical excision of the involved exit site.

Anti-Bacterial Agents↗