Showing papers by "Dale G. Renlund published in 2005"
TL;DR: Total WBC count is confirmed to be an independent predictor of death/MI in patients with or at high risk for CAD, but greater predictive ability is provided by high N (Q4 >6.6 x 10(3)/microl) or low L counts.
848 citations
TL;DR: MMF reduces mortality and graft loss up to 36 months after transplantation and in patients undergoing intravascular ultrasound, the change in mean maximal intimal thickness was less for the MMF group than for the AZA group.
Abstract: Background This study reports the 36-month results of a randomized, double-blind, active-controlled trial of mycophenolate mofetil (MMF) vs azathioprine (AZA) in heart transplant patients. Methods Patients were randomized at the time of transplant to receive MMF (1,500 mg twice a day, N = 327) or AZA (1.5 to 3 mg/kg in 4 daily doses, N = 323) in addition to cyclosporine and corticosteroids; 289 patients in each group received study drug. Data were analyzed in all randomized patients (enrolled) and in patients who received study medications (treated). Clinical and graft assessments continued for 36 months. Results For the co-primary end-point, 53 of 289 (18.3%) AZA-treated patients either died or received another transplant compared with 34 of 289 (11.8%) MMF-treated patients ( p p = 0.029). In patients undergoing intravascular ultrasound, the change in mean maximal intimal thickness was less for the MMF group than for the AZA group (0.06 ± 0.03 mm vs 0.13 ± 0.03 mm, respectively; p = 0.056). No significant differences between treatments were observed in quantitative coronary angiographic measurements of transplant coronary vasculopathy. Congestive heart failure, atrial arrhythmia and leukopenia were more common in the AZA group, whereas diarrhea, esophagitis, Herpes simplex , Herpes zoster and cytomegalovirus (CMV) tissue invasion were more common in MMF-treated patients. Conclusion MMF reduces mortality and graft loss up to 36 months after transplantation.
230 citations
TL;DR: In cardiac transplant recipients, PCI with stents can be performed with high rates of primary success and a trend toward less restenosis with drug-eluting stents was observed, which needs to be confirmed in larger studies.
Abstract: Background Allograft coronary vasculopathy is a major cause of death beyond the first year after cardiac transplantation. The aim of this study was to review our experience with percutaneous coronary intervention (PCI) with stents in cardiac transplant recipients. Methods We identified patients who were treated with PCI using stents. Patient characteristics, procedure information and clinical outcomes were assessed for these patients by review of their medical records. We also compared results for those who had bare metal stents vs those who had drug-eluting stents. Results Forty patients from our program's 865 cardiac transplant recipients received a total of 78 coronary stents. There were 35 males (87.5%) and 5 females (12.5%). The indication for PCI was progressive asymptomatic coronary vasculopathy in 18 patients (45%), angina in 5 (12.5%), acute myocardial infarction (MI) in 4 (10%) and congestive heart failure (CHF) in 6 (15%). Primary success ( p = 0.27). Conclusions In cardiac transplant recipients, PCI with stents can be performed with high rates of primary success. Restenosis rates are higher compared with PCI in native coronary arteries. A trend toward less restenosis with drug-eluting stents was observed, which needs to be confirmed in larger studies.
74 citations
TL;DR: This study examined the database of biopsy findings where histologic vascular parameters as well as immunofluorescence to detect AMR to determine whether VASC and ENDO are adequate to act as screening parameters to trigger further AMR investigation.
Abstract: Background Diagnostic criteria for antibody-mediated rejection (AMR) of the cardiac allograft have recently been proposed as part of the International Society for Heart and Lung Transplantation (ISHLT) biopsy grading scheme. Histologic features of vascular adherence of macrophages (VASC) and endothelial activation or swelling in capillaries (ENDO) are proposed as criteria to prompt the immunohistochemical investigation of biopsies for AMR. The aim of this study was to determine whether VASC and ENDO are adequate to act as screening parameters to trigger further AMR investigation. Methods We examined our database of biopsy findings where histologic vascular parameters as well as immunofluorescence (IF) to detect AMR were collected ( n = 3,170). Histologic parameters were graded semi-quantitatively on a scale from 1 to 5, where 1=absence and 5=obvious and generalized presence of the finding. Results Seven hundred sixty-eight of 3,170 biopsies had IF findings diagnostic of AMR in the absence of cellular rejection (ISHLT = 0). ENDO had a sensitivity of 63% and a specificity of 80%. VASC had a sensitivity of 30% and specificity of 99%. Combining the interpretation of the 2 tests did not result in a significant improvement of test sensitivity. Conclusions Neither ENDO, VASC nor the combination of the tests indicated sufficiently high sensitivity to serve as a screening tool before further diagnostic investigation for AMR. Immunohistochemical testing remains necessary in the majority of cases to identify AMR.
68 citations
TL;DR: The GRS method detected significant differences in CAD by GRS group, whereas separate genotypes did not, suggesting that such approaches deserve further examination in common, complex diseases such as CAD.
Abstract: While previous results of genetic association studies for common, complex diseases (eg., coronary artery disease, CAD) have been disappointing, examination of multiple related genes within a physiologic pathway may provide improved resolution. This paper describes a method of calculating a genetic risk score (GRS) for a clinical endpoint by integrating data from many candidate genes and multiple intermediate phenotypes (IPs). First, the association of all single nucleotide polymorphisms (SNPs) to an IP is determined and regression beta-coefficients are used to calculate an IP-specific GRS for each individual, repeating this analysis for every IP. Next, the IPs are assessed by a second regression as predictors of the clinical endpoint. Each IP's individual GRS is then weighted by the regression beta-coefficients from the second step, creating a single, composite GRS. As an example, 3,172 patients undergoing coronary angiography were evaluated for 3 SNPs from the cholesterol metabolism pathway. Although these data provide only a preliminary example, the GRS method detected significant differences in CAD by GRS group, whereas separate genotypes did not. These results illustrate the potential of the GRS methodology for multigenic risk evaluation and suggest that such approaches deserve further examination in common, complex diseases such as CAD.
67 citations
TL;DR: The GRS method detected significant differences in CAD by GRS group, whereas separate genotypes did not, suggesting that such approaches deserve further examination in common, complex diseases such as CAD.
Abstract: While previous results of genetic association studies for common, complex diseases (eg., coronary artery disease, CAD) have been disappointing, examination of multiple related genes within a physiologic pathway may provide improved resolution. This paper describes a method of calculating a genetic risk score (GRS) for a clinical endpoint by integrating data from many candidate genes and multiple intermediate phenotypes (IPs). First, the association of all single nucleotide polymorphisms (SNPs) to an IP is determined and regression β‐coefficients are used to calculate an IP‐specific GRS for each individual, repeating this analysis for every IP. Next, the IPs are assessed by a second regression as predictors of the clinical endpoint. Each IP's individual GRS is then weighted by the regression β‐coefficients from the second step, creating a single, composite GRS. As an example, 3,172 patients undergoing coronary angiography were evaluated for 3 SNPs from the cholesterol metabolism pathway. Although these data provide only a preliminary example, the GRS method detected significant differences in CAD by GRS group, whereas separate genotypes did not. These results illustrate the potential of the GRS methodology for multigenic risk evaluation and suggest that such approaches deserve further examination in common, complex diseases such as CAD.
58 citations
TL;DR: Three‐year survival rates paradoxically improved for patients with increasing BMI, and survival rates for the larger three BMI quartiles were significantly better than for the lowest quartile after adjusting for severity of illness, age, and gender.
Abstract: Purpose
Heart failure (HF) patients often have comorbid conditions that confound management and adversely affect prognosis. The purpose of this study was to determine whether the obesity paradox is also present in hospitalized HF patients in an integrated healthcare system.
Data sources
A cohort of 2707 patients with a primary diagnosis of HF was identified within an integrated, 20-hospital healthcare system. Patients were identified by ICD-9 codes or a left ventricular ejection fraction ≤40% dating back to 1995. Body mass index (BMI) was calculated using the first measured height and weight when hospitalized with HF. Survival rates were calculated using Kaplan Meier estimation. Hazard ratios for 3-year mortality with 95% confidence intervals were assessed using Cox regression, controlling for age, gender, and severity of illness at time of diagnosis.
Conclusions
Three-year survival rates paradoxically improved for patients with increasing BMI. Survival rates for the larger three BMI quartiles were significantly better than for the lowest quartile after adjusting for severity of illness, age, and gender.
Implications for practice
While obesity increases the risk of developing HF approximately twofold, reports involving stable outpatients suggest that obesity is associated with improved survival after the development of HF. This finding is paradoxical because obesity increases the risk and worsens the prognosis of other cardiovascular diseases.
50 citations
TL;DR: It was found that statin use before diagnosis was not significantly greater in patients than controls (odds ratio 1.30, 95% confidence interval 0.3 to 2.1), nor were doses different between patients and controls.
Abstract: A recent European case-control study suggested that statins increase the risk for polyneuropathy, a rare but serious neurologic condition. This risk was assessed in 272 patients with idiopathic polyneuropathy and 1,360 matched controls in the Intermountain Health Care electronic database. It was found that statin use before diagnosis was not significantly greater in patients than controls (odds ratio 1.30, 95% confidence interval 0.3 to 2.1, p = 0.27), nor were doses different between patients and controls.
26 citations
TL;DR: After orthotopic heart transplantation, TVR is a safe and effective procedure to alleviate RHF symptoms and flail leaflets are the most common operative finding, suggesting that biopsy-induced trauma is the likely cause of severe TI in these patients.
Abstract: Background Tricuspid valve insufficiency (TI) is common after orthotopic heart transplantation. However, tricuspid valve replacement or repair (TVR) is rare. The aim of this study is to evaluate our experience with TVR in cardiac transplant recipients. Methods The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program database was queried for TVR in all adult and pediatric heart transplant recipients. Pre-operative parameters and cardiac hemodynamics were compared with post-operative findings. Results Since 1985, we identified in our database 17 patients who had 16 TVR, and 2 tricuspid valve repair procedures. Thirty-four heart transplant recipients from the same period were used as controls. The indication for TVR was symptomatic right heart failure (RHF) in 89% of cases, and there was no significant difference between the control group and the surgery group in the average number of biopsies. A flail leaflet was found in 16 cases (89%). One patient died post-operatively due to cardiogenic shock, and 1 patient died 8 months after TVR due to progressive RHF. Improvement in heart failure symptoms was seen in 12 cases. The central venous pressure (CVP) decreased from 17.8 ± 4.1 mm Hg to 11.0 ± 7.3 mm Hg ( p = 0.013). There was no significant change in cardiac output or renal function. However, the furosemide dose decreased significantly from 47.69 ± 56.44 mg/day to 26.54 ± 46.43 mg/day ( p = 0.009). Conclusions After orthotopic heart transplantation, TVR is a safe and effective procedure to alleviate RHF symptoms. Flail leaflets are the most common operative finding, suggesting that biopsy-induced trauma is the likely cause of severe TI in these patients.
25 citations
TL;DR: It is suggested that patients who have coronary artery disease without these conditions have approximately the same protective benefit against death as those who have HF or AMI.
Abstract: Beta-blocker therapy has been shown to benefit patients who have coronary artery disease and present with acute myocardial infarction (AMI) and/or congestive heart failure (HF). However, whether β-blocker therapy provides a similar benefit in patients who have coronary artery disease but not AMI or HF is unknown. A population of 4,304 patients who did not have HF but did have angiographically confirmed coronary artery disease (≥1 stenosis of ≥70%) without AMI at hospital presentation was evaluated. Baseline demographics, cardiac risk factors, clinical presentation, therapeutic procedures, and discharge medications were recorded. Patients were followed for a mean of 3.0 ± 1.9 years (range 1 month to 6.9 years) for outcomes of all-cause death or AMI. Patients' average age was 65 ± 11 years and 77% were men. Overall, 10% died and 5% had a nonfatal AMI. Discharge β-blocker prescription was associated with an increased event-free AMI survival rate for all-cause death (no β blocker 88.3%, β blocker 94.5%, p
25 citations
TL;DR: Early postoperative use of ENOX and UFH is associated with a significant increase in re-exploration for postoperative bleeding, often at a significantly delayed time period after the initial surgery.
TL;DR: Even in the absence of coronary artery disease, patients with left ventricular dysfunction are at increased risk of mortality based on their baseline CRP concentrations, and patients with high CRP levels independently predicted mortality.
Abstract: C-reactive protein (CRP) has been associated with atherosclerotic complications, and we hypothesized that CRP levels might also predict death in non-ischemic patients with left ventricular dysfunction
TL;DR: Because HF care now incorporates increasingly complicated strategies and technologies, and because the number of HF patients is burgeoning, capable and specialized providers are needed.
TL;DR: A survival benefit was observed in pts that received MAWDSbased SMI and a comparison cohort of 1,041 pts without documented SMI of any kind were tracked for 2 years after discharge.
Abstract: Background: In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) mandated that hospitalized heart failure (HF) patients (pts) receive self-management instruction (SMI) before discharge. SMI was implemented in a 20-hospital, non-profit, integrated health care system and tracked by an electronic data system. We hypothesized that hospital-based SMI could be implemented successfully leading to improved outcomes. Methods: An SMI tool called MAWDS was developed that focused on HF instructions and monitoring of pt medications, activity, weight, diet, symptoms and when to call a provider for assistance. Providers and nurses were trained on the use of the tool, then nurses began formal SMI and tool delivery to hospitalized HF pts. Results: 745 pts who had documented formal MAWDS instruction and a comparison cohort of 1,041 pts without documented SMI of any kind were tracked for 2 years after discharge. After adjustments for age, length of stay, severity of illness, and gender, a survival benefit was observed (p 0.0002, RR 0.66) in pts that received MAWDSbased SMI.
TL;DR: This large prospective study demonstrates that, in addition to a general improvement in procedural success and a reduced need for repeat revascularization, the use of stents with dual antiplatelet therapy was associated with a significant reduction in long-term mortality.
TL;DR: At this centre the introduction of cyclosporine profiling and the regular use of C0 and C2 monitoring have improved the results in terms of reducing the number of significant biopsy proven rejection episodes and reducing theNumber of cyclOSporine related side effects.
Abstract: between the mean number of grade 3 rejection episodes between the groups (group 1 0.52 0.1 and group 2 1.68 2.5) p 0.018. There was also a trend towards giving lower doses of CsA in Group 1 (244 mg) compared with Group 2 (293 mg) p 0.06. The number of patients who were switched from cyclosporine to an alternative immunosuppressant agent on clinical grounds (neurotoxicity or two or more episodes of early rejection) were also significantly higher in group 2. Conclusions: At our centre the introduction of cyclosporine profiling and the regular use of C0 and C2 monitoring have improved our results in terms of reducing the number of significant biopsy proven rejection episodes and reducing the number of cyclosporine related side effects.