Search PubMed⌕ Search

Biomedical subjects

Lynne E Wagoner

Publications and source records attributed to Lynne E Wagoner.

18 recordsLinked to original sources
PubMed2006

A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure.

Heterogeneity of heart failure (HF) phenotypes indicates contributions from underlying common polymorphisms. We considered polymorphisms in the beta(1)-adrenergic receptor (beta(1)AR), a beta-blocker target, as candidate pharmacogenomic loci. Transfected cells, genotyped human nonfailing and failing ventricles, and a clinical trial were used to ascertain phenotype and mechanism. In nonfailing and failing isolated ventricles, beta(1)-Arg-389 had respective 2.8 +/- 0.3- and 4.3 +/- 2.1-fold greater agonist-promoted contractility vs. beta(1)-Gly-389, defining enhanced physiologic coupling under relevant conditions of endogenous expression and HF. The beta-blocker bucindolol was an inverse agonist in failing Arg, but not Gly, ventricles, without partial agonist activity at either receptor; carvedilol was a genotype-independent neutral antagonist. In transfected cells, bucindolol antagonized agonist-stimulated cAMP, with a greater absolute decrease observed for Arg-389 (435 +/- 80 vs. 115 +/- 23 fmol per well). Potential pathophysiologic correlates were assessed in a placebo-controlled trial of bucindolol in 1,040 HF patients. No outcome was associated with genotype in the placebo group, indicating little impact on the natural course of HF. However, the Arg-389 homozygotes treated with bucindolol had an age-, sex-, and race-adjusted 38% reduction in mortality (P = 0.03) and 34% reduction in mortality or hospitalization (P = 0.004) vs. placebo. In contrast, Gly-389 carriers had no clinical response to bucindolol compared with placebo. Those with Arg-389 and high baseline norepinephrine levels trended toward improved survival, but no advantage with this allele and exaggerated sympatholysis was identified. We conclude that beta(1)AR-389 variation alters signaling in multiple models and affects the beta-blocker therapeutic response in HF and, thus, might be used to individualize treatment of the syndrome.

Adrenergic beta-Antagonists↗
PubMed2005

Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation.

It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field.

Female↗
PubMed2004

Prevalence of obstructive sleep apnoea and periodic limb movement in 45 subjects with heart transplantation.

BACKGROUND: Obesity, a major risk factor for obstructive sleep apnoea, is common after cardiac transplantation. Case reports have shown development of obstructive sleep apnoea in cardiac transplantation recipients. The present study represents the first systematic evaluation of sleep disorders after cardiac transplantation. OBJECTIVE: To determine the prevalence and clinical impact of sleep disorders in a cohort of cardiac transplant recipients. METHODS: This was a cross-sectional study at the Veterans Affairs Medical Center. Forty-five of 60 eligible subjects agreed to take part in the study. Polysomnography, sleep and health survey questionnaires, and laboratory tests were recorded. RESULTS: Thirty-six percent had obstructive sleep apnoea-hypopnoea with an index of 15 or more per hour. The average apnoea-hypopnoea index was about 50+/-27 (SD) per hour. Sleep apnoea resulted in arterial oxyhaemoglobin desaturation, excessive arousals, unrefreshing sleep, excessive daytime sleepiness, poor health-related quality of life, and hypertension (all P values <0.05). Weight gain since transplantation was significantly greater in recipients with obstructive sleep apnoea than those without. Thirty-three percent of patients had periodic limb movement with an index of >?15/hour and an average of 55+/-43/hour. Forty-five percent of these patients had restless legs syndrome. CONCLUSION: Thirty-six percent of cardiac transplant recipients have moderate to severe obstructive sleep apnoea. Sleep apnoea results in disrupted sleep, desaturation and impaired quality of life. Polysomnography should be routinely considered in the ongoing management of most cardiac transplant recipients. Treatment of obstructive sleep apnoea may improve quality of life and other outcomes of cardiac transplantation.

Cohort Studies↗
PubMed2004

Strongyloides hyperinfection syndrome after heart transplantation: case report and review of the literature.

Stronglyoides hyperinfection syndrome (SHS) is an augmentation of the infective life cycle of S stercoralis. Immunosuppressed patients, especially those taking corticosteroid therapy, are at risk. We present a case of fatal SHS with disseminated infection following orthotopic heart transplantation. The patient was treated with increased doses of immunosuppressive medications for graft rejection, including corticosteroids. A review of the literature describing the pathophysiology, host defenses and treatment of SHS is also presented. Diagnostic tests for S stercoralis are reviewed. SHS should be part of the differential diagnosis in immunosuppressed patients presenting with sepsis or gastrointestinal or pulmonary complaints. Pretransplant evaluation for parasitic infections, including strongyloidiasis, should occur in endemic areas or in patients at risk for occult infestation.

Bronchoalveolar Lavage Fluid↗
PubMed2004

Recurrent primary cardiac malignant fibrous histiocytoma following orthotopic heart transplantation.

Malignant fibrous histiocytoma (MFH) is an extremely rare primary cardiac tumor. We describe a young patient who underwent orthotopic heart transplantation for an unresectable right ventricular MFH and presented 7 years later with a local recurrence in the native right atrium. This was treated by complete resection of the right atrial tumor and adjuvant chemotherapy. This case represents the only reported long-term survival following cardiac transplantation for MFH and describes our management strategy for local recurrence in this patient.

Adult↗
PubMed2003

Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes.

BACKGROUND: IL-5 is a cytokine critically involved in regulating several aspects of eosinophils including their production, activation, and tissue recruitment. As such, IL-5 may be involved in the pathogenesis of hypereosinophilic syndromes, a group of poorly treated diverse disorders characterized by sustained peripheral blood and/or tissue eosinophilia. OBJECTIVE: We aimed to assess the safety and efficacy of a humanized blocking monoclonal antibody against IL-5 (mepolizumab) in patients with several forms of hyper-eosinophilic syndromes. METHODS: We performed an open-label trial of anti-IL-5 in which 3 intravenous doses (10 mg/kg, maximum 750 mg) were administered at 4-week intervals to 4 patients with hypereosinophilic syndromes (defined by peripheral blood and/or tissue eosinophilia). The effects of treatment on safety, eosinophil levels (in peripheral blood and/or diseased tissue), pulmonary function, and quality of life were measured over a 28-week period. RESULTS: Anti-IL-5 was well tolerated in all patients and lowered peripheral blood eosinophil counts despite ongoing systemic glucocorticoid therapy. The decline in circulating eosinophil counts was sustained for at least 12 weeks after the last dose of anti-IL-5. In addition, anti-IL-5 improved clinical and quality of life measurements. In one patient with striking tissue eosinophilia (eosinophilic esophagitis), anti-IL-5 resulted in a 10-fold reduction in tissue eosinophil levels. CONCLUSIONS: These results suggest that anti-IL-5 is safe, effective in lowering eosinophil levels, and has potential glucocorticoid-sparing effects in patients with a variety of hyper-eosinophilic syndromes. As such, anti-IL-5 may have significant therapeutic potential for hypereosinophilic syndromes.

Adolescent↗
PubMed2003

Beta 1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure.

Catecholamines stimulate cardiac contractility through beta(1)-adrenergic receptors (beta(1)-ARs), which in humans are polymorphic at amino acid residue 389 (Arg/Gly). We used cardiac-targeted transgenesis in a mouse model to delineate mechanisms accounting for the association of Arg389 with human heart failure phenotypes. Hearts from young Arg389 mice had enhanced receptor function and contractility compared with Gly389 hearts. Older Arg389 mice displayed a phenotypic switch, with decreased beta-agonist signaling to adenylyl cyclase and decreased cardiac contractility compared with Gly 389 hearts. Arg389 hearts had abnormal expression of fetal and hypertrophy genes and calcium-cycling proteins, decreased adenylyl cyclase and G alpha(s) expression, and fibrosis with heart failure This phenotype was recapitulated in homozygous, end-stage, failing human hearts. In addition, hemodynamic responses to beta-receptor blockade were greater in Arg389 mice, and homozygosity for Arg389 was associated with improvement in ventricular function during carvedilol treatment in heart failure patients. Thus the human Arg389 variant predisposes to heart failure by instigating hyperactive signaling programs leading to depressed receptor coupling and ventricular dysfunction, and influences the therapeutic response to beta-receptor blockade.

Adrenergic beta-Antagonists↗
PubMed2003

Infections in the heart transplant recipient.

The overall incidence of infection after transplantation has decreased with improved immunosuppressive agents, increased knowledge and use of prophylaxis, and better detection and treatment of infection. Nevertheless, infection continues to be a major cause of morbidity and mortality in heart transplant recipients. The knowledgeable nurse in any setting who cares for a transplant recipient must be aware of the lifelong susceptibility to common and opportunistic infections. The transplant recipient and his or her family must also be aware of the risks of early opportunistic infection. Infection is a lifelong concern for all persons on immunosuppressant medications, and the individual must learn appropriate precautions to reduce this risk. Hand washing and avoidance of infected individuals are the most important self-care actions that the transplant patient should adopt. Recipients must also learn to monitor for subtle signs of infection. The nurse is responsible for teaching self-care to patients and family members. Ultimately, a team effort by the patient, family, nurses, and physicians can reduce the risk of infection in this vulnerable population.

Female↗
PubMed2003

Sympathetic nervous system function as measured by I-123 metaiodobenzylguanidine predicts transplant-free survival in heart failure patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Heightened activity of the sympathetic nervous system in heart failure patients is a major contributor to disease progression and death. I-123 metaiodobenzylguanidine (MIBG) provides an accurate, noninvasive method to assess cardiac sympathetic nerve activity. METHODS: Thirty-seven patients with New York Heart Association class II, III, or IV heart failure underwent baseline measurement of I-123 MIBG heart-to-mediastinum ratios, maximum oxygen consumption, radionuclide left ventricular ejection fraction, and plasma norepinephrine levels. Patients were followed 48.8+/-8.6 months to endpoints of cardiac death or transplantation. The heart-to-mediastinum ratio of I-123 MIBG activity measured 15 minutes after injection was the only independent predictor of transplant-free survival (P<.0001). I-123 MIBG imaging at 15 minutes identified patients with subsequent cardiac transplantation or death with a sensitivity of 92% and specificity of 72%, whereas the corresponding values for maximum oxygen consumption were 75% and 56%. By Kaplan-Meier survival analysis, the time to a cardiac endpoint was significantly shorter in patients with a 15-minute I-123 MIBG heart-to-mediastinum ratio below the group mean ratio of 1.536, compared with patients with a preserved I-123 MIBG ratio. Maximum oxygen consumption was not predictive of time to cardiac transplant or death. CONCLUSIONS: In this study of patients with congestive heart failure resulting from dilated cardiomyopathy, a 15-minute heart-to-mediastinum ratio of I-123 MIBG activity provided more accurate prediction of cardiac transplantation or death than other standard clinical tests.

3-Iodobenzylguanidine↗
PubMed2003

Facilitating heart transplant candidate evaluation throughout Ohio.

The Ohio Solid Organ Transplantation Consortium (OSOTC) has a mission to ensure equitable access to transplant services to those most likely to benefit, regardless of personal resources. Patients are selected according to criteria established by the OSOTC, which are delineated in the Ohio Department of Health rule, and consistent with national criteria. The University of Cincinnati's Institute for Health Policy and Health Services Research (IHPHSR) has implemented a secure internet-based system to replace the OSOTC's existing fax-based procedures. This system meets both the patient evaluation and basic research needs of the OSOTC.

Heart Transplantation↗
PubMed2002

Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure.

BACKGROUND: Sustained cardiac adrenergic stimulation has been implicated in the development and progression of heart failure. Release of norepinephrine is controlled by negative feedback from presynaptic alpha2-adrenergic receptors, and the targets of the released norepinephrine on myocytes are beta1-adrenergic receptors. In transfected cells, a polymorphic alpha2C-adrenergic receptor (alpha2CDel322-325) has decreased function, and a variant of the beta1-adrenergic receptor (beta1Arg389) has increased function. We hypothesized that this combination of receptor variants, which results in increased synaptic norepinephrine release and enhanced receptor function at the myocyte, would predispose persons to heart failure. METHODS: Genotyping at these loci was performed in 159 patients with heart failure and 189 controls. Logistic-regression methods were used to determine the potential effect of each genotype and the interaction between them on the risk of heart failure. RESULTS: Among black subjects, the adjusted odds ratio for heart failure among persons who were homozygous for alpha2CDel322-325 as compared with those with the other alpha2C-adrenergic receptor genotypes was 5.65 (95 percent confidence interval, 2.67 to 11.95; P<0.001). There was no increase in risk with beta1Arg389 alone. However, there was a marked increase in the risk of heart failure among persons who were homozygous for both variants (adjusted odds ratio, 10.11; 95 percent confidence interval, 2.11 to 48.53; P=0.004). The patients with heart failure did not differ from the controls in the frequencies of nine short tandem-repeat alleles. Among white subjects, there were too few who were homozygous for both polymorphisms to allow an adequate assessment of risk. CONCLUSIONS: The alpha2CDel322-325 and beta1Arg389 receptors act synergistically to increase the risk of heart failure in blacks. Genotyping at these two loci may be a useful approach for identification of persons at risk for heart failure or its progression, who may be candidates for early preventive measures.

Adult↗
PubMed2002

Polymorphisms of the beta1-adrenergic receptor predict exercise capacity in heart failure.

BACKGROUND: Exercise performance in patients with congestive heart failure is partially dependent on cardiac beta1-adrenergic receptor (beta1AR) function. There are 2 common polymorphisms of the beta1AR gene that alter the encoded amino acids at positions 49 (Ser or Gly) and 389 (Gly or Arg) and alter receptor function in vitro. Their relevance to modification of cardiac function in heart failure is not known. METHODS: Exercise testing was performed in 263 patients with idiopathic or ischemic cardiomyopathy (left ventricular ejection fraction approximately 25%). Potential associations were sought between beta1AR genotypes and the primary outcome variables of peak oxygen consumption (VO2), heart rate response, and exercise time. RESULTS: The major determinants of exercise capacity were the polymorphisms at position 389, where patients homozygous for Gly389 had significantly lower peak VO2 compared with those with Arg389 (14.5 +/- 0.6 vs 17.7 +/- 0.4 mL/kg/min, P =.006), despite similar clinical characteristics including left ventricular ejection fraction. Consistent with a gene dose-response, heterozygosity was associated with an intermediate response (16.9 +/- 0.6 mL/kg/min, P <.05). When position 49 genotypes were included, a graded relationship between the 5 2-locus haplotypes and VO2 was found. Two haplotypes displayed the most divergent peak VO2: homozygous Gly389/Ser49, and homozygous Arg389/Gly49 carriers (14.4 +/- 0.5 vs 18.2 +/- 0.8 mL/kg/min, P =.001). Genotype did not predict the heart rate response. The above results were independent of beta-blocker or other medication use, left ventricular ejection fraction, beta2AR genotype, or other demographic and clinical characteristics. CONCLUSION: beta1AR polymorphisms are a significant determinant of exercise capacity in patients with congestive heart failure. Early identification, by genetic testing for these polymorphisms, of heart failure patients at risk for development of depressed exercise capacity may be useful for initiation of specific therapy tailored to genotype.

Cardiomyopathy, Dilated↗
PubMed2002

The challenge of managing the care of older heart transplant recipients.

Age is perhaps the most controversial exclusion criterion for heart transplantation. One concern focuses on whether chronological or functional age is the better predictor of positive outcomes when considering heart transplantation for an elderly patient with end-stage heart disease. Another concern is related to the philosophical and ethical rationale for allocation of scarce resources to those near the end of a normal life expectancy. However, the number of people who are older than age 65 years and have received a donor heart has increased and will continue to due to aging of the people who received a transplant a decade ago, as well as the growing number of people who undergo heart transplantation after the age of 65. In either case, the nurse must be aware of age-related concerns in this vulnerable population.

Age Factors↗
PubMedDate not supplied

Activity of the uptake-1 norepinephrine transporter as measured by I-123 MIBG in heart failure patients with a loss-of-function polymorphism of the presynaptic alpha2C-adrenergic receptor.

BACKGROUND: Patients with a deletion of 4 consecutive amino acids in the gene encoding for the alpha(2C)-adrenergic receptor (alpha(2C)Del322-325) have an increased prevalence of clinical heart failure, worse clinical status, and a lower left ventricular ejection fraction compared with patients without this deletion. We postulated that patients with the alpha(2C)Del322-325 polymorphism would have a compensatory increase in norepinephrine uptake-1 transporter activity as measured by iodine 123 metaiodobenzylguanidine (MIBG). METHODS AND RESULTS: Thirty-nine patients with heart failure related to idiopathic dilated cardiomyopathy were studied. Demographic characteristics, left ventricular ejection fraction, maximum oxygen consumption, exercise duration, and plasma norepinephrine levels did not differ between patients with the alpha(2C) receptor polymorphism (n = 9) and those without it (n = 30). Patients with the alpha(2C)Del322-325 polymorphism had significantly greater heart-to-mediastinum ratios of I-123 MIBG at 4 hours after tracer injection (1.60 +/- 0.19 vs 1.41 +/- 0.19, P =.0117) and greater background-corrected heart counts per pixel at 4 hours compared with patients without the polymorphism. CONCLUSIONS: Patients with genetic impairment of the alpha(2C)-adrenergic receptor have augmented activity of the norepinephrine uptake-1 transporter as measured by I-123 MIBG. Further studies are needed to clarify the mechanism by which uptake-1 transporter activity is increased in this setting.

3-Iodobenzylguanidine↗
PubMedDate not supplied

Carvedilol improves left ventricular function in heart failure patients with idiopathic dilated cardiomyopathy and a wide range of sympathetic nervous system function as measured by iodine 123 metaiodobenzylguanidine.

BACKGROUND: Carvedilol treatment reduces the mortality rate in patients with congestive heart failure. It is not known whether carvedilol treatment is effective in heart failure patients with substantial cardiac sympathetic nerve dysfunction. The goal of this study was to determine the effect of chronic carvedilol treatment in patients with cardiac sympathetic nerve dysfunction of varying severity. METHODS AND RESULTS: In 22 congestive heart failure patients with idiopathic cardiomyopathy, sympathetic nerve function was assessed before and after 7.2 +/- 2.7 months of carvedilol treatment with the use of iodine 123 metaiodobenzylguanidine (MIBG) imaging, radionuclide ventriculography, and transmyocardial norepinephrine sampling. Patients with relatively advanced impairment of cardiac sympathetic nerve function, as manifested by a baseline I-123 MIBG ratio lower than 1.40, had a statistically significant improvement in I-123 heart-mediastinum ratio with carvedilol treatment, from 1.26 +/- 0.12 to 1.39 +/- 0.20 (P =.004). Of 10 patients with a baseline I-123 MIBG ratio lower than 1.40, 9 had an increase in the heart-mediastinum ratio with carvedilol treatment. Left ventricular ejection fraction increased from 25.4% +/- 7.8% to 37.3% +/- 14.7% (P <.001), with no difference between patients with relatively advanced versus relatively preserved cardiac sympathetic nerve function. CONCLUSION: Most patients with congestive heart failure show a favorable response in left ventricular function to carvedilol treatment, regardless of the baseline level of cardiac sympathetic nervous system function, as assessed by neuronal imaging with I-123 MIBG. Patients with relatively advanced impairment of baseline I-123 MIBG uptake are most likely to show evidence of improved cardiac sympathetic nervous system function in response to carvedilol therapy.

3-Iodobenzylguanidine↗
PubMedDate not supplied

An exploratory study of body awareness in persons with heart failure treated medically or with transplantation.

Heart failure is a chronic disabling problem afflicting a growing number of adults. These individuals experience episodes of exacerbation demonstrated by increasing shortness of breath, fatigue, and fluid retention. The symptoms often develop in a slow and insidious manner making perception of worsening difficult to determine. Theoretically, an increase in body awareness may help individuals recognize symptoms of worsening heart failure earlier, but it is not known whether increased body awareness leads to somatization, an abnormal dwelling on body symptoms. This study was conducted to describe body awareness in 90 persons with heart failure or after transplant. We found that the Body Awareness Quesionnaire was a reliable measure of this concept in this sample. When body awareness was examined for age, gender, and treatment (HF or transplant) group were examined, no significant differences were found. Furthermore, there were no significant relationships between body awarenss and negative moods such as anxiety, depression, or anger. Interventions to enhance body awareness may be a fruitful new direction that will improve symptom recognition without increasing somatization in persons with heart failure.

Affect↗
PubMedDate not supplied

Emergency department observation of heart failure: preliminary analysis of safety and cost.

Emergency-department (ED)-based observation-unit treatment has been shown to reduce inpatient admissions, hospital bed-hours, and costs without adversely affecting outcomes for several conditions. A sequential group design study compared risk-matched, acute decompensated heart failure patients admitted directly to the inpatient setting with those admitted to an ED observation unit for up to 23 hours before ED disposition. Outcomes were 30-day readmissions or repeat ED visits for heart failure or 30-day mortality. Estimates of bed-hours and charges between the groups were compared. Sixty-four patients were enrolled with 36 inpatient admissions and 28 observation unit patients. No patients died within 30 days. Observation unit patients had no significant difference in outcomes, a decrease in time from ED triage to discharge, a saving in mean bed-hours, and less total charges. This pilot trial provides preliminary data that suggest admitted, low-risk heart failure patients may be safely and cost-effectively managed in an ED-based observation unit. These findings need to be further evaluated in a randomized clinical trial.

Case-Control Studies↗