PubMed Health⌕ Search

Biomedical subjects

James A Hill

Publications and source records attributed to James A Hill.

At least 19 recordsLinked to original sources
PubMed2006

Relation of beta(2)-adrenoceptor haplotype to risk of death and heart transplantation in patients with heart failure.

Heart failure (HF) is characterized by neurohormonal activation of the sympathetic nervous and renin-angiotensin systems. Genetic polymorphisms in these systems could alter the prognosis in HF. We hypothesized the genetic polymorphisms in the sympathetic nervous and renin-angiotensin systems are associated with adverse outcomes, defined as death or heart transplantation in patients with HF. A total of 227 patients with HF were enrolled from a tertiary care clinic and followed for outcomes for < or =4 years. Eight polymorphisms in 6 genes were genotyped: beta(1)-adrenergic receptor (ADRB1, S49G, R389G), beta(2)-adrenergic receptor (ADRB2, G16R, Q27E), alpha(2c)-adrenergic receptor (ADRA2C, insertion/deletion 322-325), angiotensinogen (AGT, M235T), angiotensin receptor type 1 (AGTR1, 1166A>C), and angiotensin-converting enzyme (ACE, insertion/deletion in intron 16). Most patients were treated according to consensus guidelines. Male gender (hazard ratio 2.24, 95% confidence interval 1.27 to 3.94), higher New York Heart Association functional class (hazard ratio 2.54, 95% confidence interval 1.84 to 3.52), and 2 copies of ADRB2 Arg16Gln27 haplotype (hazard ratio 1.91, 95% confidence interval 1.09 to 3.36) increased the risk of adverse outcomes. In contrast, a higher serum sodium level (hazard ratio 0.91, 95% confidence interval 0.86 to 0.97) and higher creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.98 to 0.99) decreased the risk of adverse outcomes. None of the other genotypes/haplotypes were associated with adverse outcomes. In conclusion, ADRB2 Arg16Gln27 haplotype may significantly increase the risk of adverse outcomes in patients with HF receiving contemporary HF pharmacotherapy.

DNA↗
PubMed2006

Comparison of calcitonin versus calcitonin + resistance exercise as prophylaxis for osteoporosis in heart transplant recipients.

BACKGROUND: Rapid bone loss occurs early after heart transplantation. There is no standard therapeutic intervention to prevent osteoporosis in heart transplant recipients (HTR). The purpose of this study was to determine the effectiveness of a regimen combining the antiresorptive properties of nasal calcitonin with the osteogenic stimulus of resistance exercise. METHODS: Eighteen candidates for heart transplantation were randomly assigned either to a group that received calcitonin and participated in 6 months of resistance exercise (n=10) or to a group that received only calcitonin (n=8). Calcitonin therapy (200 IU daily for 8 months) was initiated 48 hr after transplantation. Resistance exercise was initiated 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck, and lumbar vertebra (L2-3) were assessed before, and at 2 and 8 months after transplantation. RESULTS: Total body and femur neck BMD did not decrease (P>or=0.05) below pretransplantation values at 2 months after transplantation in either group. BMD of the lumbar spine was significantly (P<or=0.05) and comparably decreased at 2 months after transplantation in the calcitonin (-10.1+/-1.8%) and calcitonin + training groups (-12.9+/-2.7%). At 8 months after transplantation lumbar BMD was -16.9% below pretransplant values in the calcitonin group. In contrast, lumbar BMD was restored to within 5% of pretransplant levels in the calcitonin + training group. CONCLUSIONS: Calcitonin attenuates BMD loss in the total body and femur neck but not in trabecular bone of the lumbar vertebra. Mechanical loading, through progressive resistance exercise, is an osteogenic stimulus in HTR.

Bone Density↗
PubMed2006

Beyond diuretics: management of volume overload in acute heart failure syndromes.

Diuretics are an established foundation of therapy for patients with chronic heart failure (HF) as well as for those hospitalized for treatment of acute HF syndromes. Despite the accepted use of diuretics in acute HF syndromes, treatment patterns with diuretics vary widely, and there are no data from randomized studies on the benefit of diuretics on morbidity or mortality in patients hospitalized with acute HF syndromes. Additional pharmacologic therapies that complement or replace diuretics in this setting, especially in patients with diuretic resistance, include positive inotropes, nitrovasodilators, and natriuretic peptides, but data are likewise lacking on important clinical outcomes. Ultrafiltration has also been used as a nonpharmacologic strategy to treat patients with acute HF syndromes who exhibit resistance to diuretics. Effective monitoring of volume status with newer modalities may allow more selective use of diuretics and diuretic-like modalities, but additional randomized trial data are clearly needed to establish ideal strategies to promote volume removal in acute HF syndromes.

Acute Disease↗
PubMed2005

Management of heart failure after cardiac resynchronization therapy: integrating advanced heart failure treatment with optimal device function.

Cardiac resynchronization therapy (CRT) is an established adjunctive treatment for patients with systolic heart failure (HF) and ventricular dyssynchrony. The majority of recipients respond to CRT with improvements in quality of life, New York Heart Association functional class, 6-min walk test, and ventricular function. Management of HF after CRT may include up-titration of neurohormonal blockade and an exercise prescription through cardiac rehabilitation to further improve and sustain clinical outcomes. Diagnostic data provided by the CRT device may help to facilitate and optimize treatment. Initial nonresponder rates remain problematic. We suggest a simple step-by-step management and troubleshooting strategy that integrates device function with advanced HF therapy in patients who do not initially respond to CRT. This algorithm represents a new, comprehensive, collaborative approach between the HF and electrophysiology specialists to further improve and sustain outcomes in the field of CRT.

Adrenergic beta-Antagonists↗
PubMed2005

Atrial fibrillation as a cause of left ventricular dysfunction after cardiac transplantation.

We report 3 cases of late-onset atrial fibrillation several years after cardiac transplantation, each involving left ventricular systolic dysfunction in the absence of cardiac rejection or cardiac allograft vasculopathy. Although the etiology of late-onset atrial fibrillation in cardiac transplant recipients is not clear, its presence in the absence of cardiac rejection or coronary allograft vasculopathy can result in left ventricular systolic dysfunction, and therefore should be considered in the differential diagnosis of cardiac allograft failure. The onset of atrial fibrillation years after a heart transplant is not necessarily an indication of rejection. Aggressive rate control and restoration of normal sinus rhythm may improve allograft function in such cases.

Atrial Fibrillation↗
PubMed2005

Effect of resistance exercise on skeletal muscle myopathy in heart transplant recipients.

The purpose of this study was to determine the efficacy of resistance exercise in reversing skeletal muscle myopathy in heart transplant recipients. Myopathy, engendered by both heart failure and immunosuppression with glucocorticoids, is a post-transplant complication. The sequelae of myopathic disease includes fiber-type shifts and deficits in aerobic metabolic capability. We randomly assigned patients to either 6 months of resistance exercise (training group; n = 8) or a control (control group; n = 7) group. Exercise was initiated at 2 months after transplant. Biopsy of the right vastus lateralis was performed before and after the 6-month intervention. Myosin heavy chain (MHC) composition was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biochemical assays were performed to determine citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and lactate dehydrogenase activity. There were no group differences (p >or=0.05) in MHC composition and enzymatic reserve at baseline. Improvements in the training group for citrate cynthase (+40%), 3-hydroxyacyl-CoA-dehydrogenase (+10%), and lactate dehydrogenase activity (+48%) were significantly greater (p <or=0.05) than in the control group (+10%, -15%, and +20%, respectively). Oxidative type 1 MHC isoform concentration increased significantly in the training group (+73%, p <or=0.05) but decreased in the control group (-28%; p <or=0.05). Glycolytic type 2x MHC isoform increased significantly (17%; p <or=0.05) in the control group but decreased (-33%; p <or=0.05) in the training group. This is the first study to demonstrate that resistance training elicits myofibrillar shifts from less oxidative type II fibers to more oxidative fatigue-resistant type I fibers in heart transplant recipients. Resistance exercise initiated early in the post-transplant period is efficacious in changing skeletal muscle phenotype through increases in enzymatic reserve and shifts in fiber morphology.

Adult↗
PubMed2005

Use of cardiac resynchronization therapy to optimize beta-blocker therapy in patients with heart failure and prolonged QRS duration.

A retrospective analysis was performed on 52 patients with heart failure to determine the change in beta-blocker therapy after cardiac resynchronization therapy (CRT). After 6 months of CRT, the number of patients receiving beta-blocker therapy increased from 36 to 44, with improved clinical outcomes and larger beta-blocker doses, indicating that these 2 therapies may work together to improve outcomes by allowing the use of larger doses of beta blockers while correcting ventricular dyssynchrony.

Adrenergic beta-Antagonists↗
PubMed2005

beta-Adrenergic receptor polymorphisms and responses during titration of metoprolol controlled release/extended release in heart failure.

OBJECTIVE: beta-Blockers require careful initiation and titration when used in patients with heart failure. Some patients tolerate beta-blocker therapy initiation without difficulty, whereas in other patients this period presents clinical challenges. We tested the hypothesis that polymorphisms at codons 389 (Arg389Gly) and 49 (Ser49Gly) of the beta(1)-adrenergic receptor would be associated with differences in initial tolerability of beta-blocker therapy in patients with heart failure. We also tested whether polymorphisms in the beta(2)-adrenergic receptor, G-protein alpha s subunit (G(s)alpha), and cytochrome P450 (CYP) 2D6 genes or S-metoprolol plasma concentrations were associated with beta-blocker tolerability. METHODS: Sixty-one beta-blocker-naive patients with systolic heart failure were prospectively enrolled. Patients began taking 12.5 to 25 mg metoprolol controlled release/extended release with titration every 2 weeks (as tolerated) to 200 mg/d or the maximum tolerated dose over a period of 8 to 10 weeks. Decompensation was the composite of death, heart failure hospitalization, increase in other heart failure medications, or need to discontinue metoprolol. End points were assessed during the titration period. RESULTS: The overall rate of decompensation was not different between the codon 49 or 389 genotypes. However, a significantly greater percentage of patients with the Gly389 variant required increases in heart failure medications as compared with Arg389 homozygotes (48% versus 14%, respectively; P = .006). Similarly, patients with the Ser49 homozygous genotype were significantly more likely to require increases in concomitant heart failure therapy as compared with Gly49 carriers (41% versus 11%, respectively; P = .03). Neither CYP2D6 genotypes nor metoprolol pharmacokinetics differed between patients with and those without a decompensation event. There was no association between the beta(2)-adrenergic receptor or G(s)alpha polymorphisms with decompensated heart failure. CONCLUSIONS: Patients with the Gly389 variant and Ser49Ser genotype were significantly more likely to require increases in heart failure medications during beta-blocker titration and thus may require more frequent follow-up during titration.

Cytochrome P-450 CYP2D6↗
PubMed2005

The case for selective re-issuance of medical certificates to allow pilots who have received a heart transplant to resume flying.

BACKGROUND: Cardiac transplant recipients have been regarded as not medically fit to fly an airplane. Recently, the Federal Aviation Administration decided to re-examine this policy and, in response, this study was undertaken to determine the risk of death from any cause and sudden-onset death in heart transplant recipients during the 12 months after an annual evaluation. METHODS: Of 6,510 patients undergoing primary orthotopic cardiac transplantation enrolled in the Cardiac Transplant Research Database (CTRD), 4,978 patients survived for at least 1 year and formed the basis of this study. Risk factors for death from any causes and sudden-onset death (a composite of causes of death that could conceivably result in a pilot's incapacitation) were determined during the 12-month period after an anniversary evaluation. Patients were re-entered into the analysis at each evaluation, resulting in a total of 23,575 anniversary evaluations. RESULTS: The presence of coronary allograft vasculopathy (CAV), left ventricular systolic dysfunction, history of rejection, malignancy, infection and pre-transplant insulin-dependent diabetes were associated with an increased risk of death from any cause and sudden-onset death during the 12-month period after an evaluation. Based on the absence of these risk factors, a group of heart transplant recipients could be defined with a 12-month risk of death from any cause of 1.0% and of sudden-onset death of 0.3% (which is identical to the mortality rate of a matched population from the U.S. life-table). CONCLUSION: Using these identified risk factors, a group of heart transplant recipients can be defined that are potentially medically certifiable to fly without compromising aviation safety.

Adolescent↗
PubMed2005

Early outcomes of a care coordination-enhanced telehome care program for elderly veterans with chronic heart failure.

Veterans with chronic heart failure (HF) are frequently elderly, have numerous comorbid chronic medical illnesses, frequent hospitalizations, and have high rates of cardiovascular events. Within the Veterans Health Administration (VHA), primary care providers are required to manage the majority of HF patients because access to cardiac specialty care within the VHA may be limited. We designed and implemented a care-coordinated, nurse-directed home telehealth management program for veterans with difficult-to-manage or new onset chronic systolic HF. An in-home telehealth message device was provided to the patient at enrollment, and patients received daily HF-specific education via the nurse coordinator and/or the device throughout their continuum of care. We collected demographic characteristics, clinical characteristics, and outcome data at the time of enrollment and at nearly 6 months after enrollment. A total of 92 patients were enrolled, with complete data available on 73. The mean patient age was 67 years, the mean left ventricular ejection fraction (LVEF) was 23%, and nearly all patients (99%) were men. After enrollment, significant improvements were found in blood pressure (129/73 to 119/69 mm Hg, p < 0.05), weight (196 to 192 pounds, p < 0.01), and shortness of breath rating (0-10 scale, 4.0 to 2.7, p = 0.02). Average daily doses of fosinopril (24 to 35 mg/d, p < 0.01) and metoprolol (84 to 94 mg/d, p = 0.05) were also improved. The total number of inpatient hospital days were reduced while on the home telehealth program (from 630 for the previous year to 122 for the duration of the program) with only 31% of the hospitalizations related to HF while on the program. Our nurse-directed, care coordinated home telehealth management program was associated with improved early outcomes in a group of elderly male veterans with chronic HF.

Aged↗
PubMed2005

Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy.

OBJECTIVE: Large variability exists in the improvement in left ventricular (LV) function from beta-blocker treatment. We hypothesized that polymorphisms at codon 389 (Arg389Gly) and 49 (Ser49Gly) in the beta1-adrenergic receptor (AR) gene were associated with LV reverse remodeling changes in response to beta-blocker therapy among heart failure patients. METHODS: We prospectively enrolled 61 beta-blocker naive patients with systolic heart failure. Patients underwent baseline echocardiography followed by metoprolol CR/XL. The dose was doubled on a biweekly basis up to 200 mg/day or attainment of maximum tolerated dose. Echocardiography was repeated after the patient received the target or highest tolerated dose for 3 months. RESULTS: Among patients with the Arg389Arg genotype, ejection fraction (EF) increased from 23+/-5 to 29+/-10 (P=0.008). Gly389 carriers did not demonstrate any significant change in EF (22+/-9 to 23+/-11; P=0.45). There was a significant between-group difference in EF by genotype (P=0.04). The Arg389Arg genotype was also associated with significantly greater reductions in LV end-diastolic and end-systolic diameters compared to Gly389 carriers. Patients with the Gly49 variant also had a significantly greater reduction in LV end-diastolic diameter compared to Ser49 homozygotes. Multiple regression analysis modeling revealed that the codon 389 polymorphism was a significant predictor of an improvement in EF and both codon 49 and 389 polymorphisms were significant predictors of final LV end-diastolic diameter. CONCLUSIONS: Heart failure patients with the Arg389Arg genotype and Gly49 carriers had greater improvements in LV remodeling from beta-blocker treatment.

Adrenergic beta-Antagonists↗
PubMed2004

Dobutamine-related asthma in a patient awaiting cardiac transplantation: the eosinophilic dilemma.

Long-term continuous intravenous inotrope infusion is frequently used as a pharmacologic bridge to cardiac transplantation in patients with end-stage congestive heart failure. We report a case of severe eosinophil-associated asthma after 6 weeks of therapy with the inotrope dobutamine in a patient awaiting cardiac transplantation. Review of the laboratory data revealed a steady increase in eosinophils during the period of treatment with dobutamine. Once the patient was switched to an alternative inotrope, milrinone, the eosinophil count returned to normal, and the asthma exacerbation resolved.

Asthma↗
PubMed2003

High-dose angiotensin-converting enzyme inhibition restores body fluid homeostasis in heart-transplant recipients.

OBJECTIVES: We tested the hypothesis that salt and fluid retention in heart-transplant recipients (HTRs) is caused by a failure to reflexively suppress the renin-angiotensin-aldosterone system (RAAS). BACKGROUND: It is known that extracellular fluid volume is expanded (12% to 15%) in HTRs who develop hypertension. METHODS: Responses to volume expansion were measured in eight HTRs (ages 57 +/- 6 years) and six liver-transplant recipients (LTRs) (ages 52 +/- 2 years) both before and after treatment with captopril (225 mg/day). After three days of a standardized diet, 0.154 mol/l saline was infused at 8 ml/kg/h for 4 h. Blood pressure, hormones, and renal function were monitored for 48 h. After four months, the same subjects received captopril (225 mg/day), and the protocol was repeated. RESULTS: Before captopril, saline infusion suppressed the RAAS in LTRs but not in HTRs, resulting in elimination of 86 +/- 12% versus 50 +/- 11% of the sodium load by 48-h postinfusion. Blood pressure increased only in the HTRs (+16 +/- 5/9 +/- 3 mm Hg) and remained elevated for 48 h (p < or = 0.05). After captopril, sodium elimination was comparable in the liver (87 +/- 13%) and heart groups (86 +/- 12%) and blood pressure did not change in either group. CONCLUSIONS; Heart transplant recipients have blunted diuretic and natriuretic responses to volume expansion that is mediated by their inability to suppress the RAAS. Pharmacologic suppression of the RAAS normalized defects in blood pressure and fluid homeostasis. These findings indicate that hypertension in HTRs is caused, in part, by a failure to reflexively suppress the RAAS when these patients become hypervolemic.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Sustained use of nesiritide to aid in bridging to heart transplant.

Patients with end-stage heart failure awaiting heart transplant are often maintained on continuous intravenous inotropic therapy. However, this therapy alone is often inadequate for maintenance of appropriate pulmonary artery pressure and stable clinical course. Nesiritide, B-type natriuretic peptide, is a recently released intravenous vasodilator for short-term use in patients with decompensated heart failure. This report details experience in four patients in whom this agent was used to bridge to transplant for prolonged periods (11-35 days) with added clinical benefit and without obvious tolerance. This suggests that new strategies for pretransplant management may be needed.

Adult↗
PubMed2003

Hyperhomocysteinemia in patients with heart failure referred for cardiac transplantation: preliminary observations.

BACKGROUND: Hyperhomocysteinemia is becoming recognized as a risk factor for cardiovascular disease, yet there are limited data on the prevalence of hyperhomocysteinemia in patients with heart failure. HYPOTHESIS: The purpose of this study was to examine the prevalence of hyperhomocysteinemia in patients with severe heart failure and to correlate serum homocysteine levels with factors that may affect homocysteine metabolism. METHODS: Serum homocysteine levels were measured at the time of cardiac transplant evaluation in 89 consecutive patients with severe heart failure. Homocysteine levels for patients with ischemic cardiomyopathy (ICM) were compared with levels obtained in patients with nonischemic cardiomyopathy (NICM), and homocysteine levels were correlated with demographic and hemodynamic parameters as well as functional status. RESULTS: The mean plasma homocysteine level was increased (14.3 +/- 5.3 micromol/l, normal <9.0 micromol/l) and was equivalent between patients with ICM versus NICM (14.7 +/- 5.8 micromol/l vs. 13.8 +/- 4.5 micromol/l, p = 0.44). Elevated homocysteine levels were seen in a large proportion (89%) of patients and were equally common to patients with NICM (94%) and ICM (85%). Serum homocysteine levels correlated with serum creatinine (r = 0.51, p < 0.001), with a history of diabetes (p = 0.028), and with a history of peripheral vascular disease (p = 0.045). Only 6% of patients were receiving folic acid therapy at the time of transplant referral. CONCLUSION: Hyperhomocysteinemia is common in patients with severe heart failure, and plasma homocysteine levels are uniformly elevated regardless of the etiology of heart failure. Elevated plasma homocysteine levels are likely a consequence of heart failure-related renal insufficiency.

Biomarkers↗
PubMed2003

Vascular effects of sildenafil in hypertensive cardiac transplant recipients.

BACKGROUND: Sildenafil is commonly used in the treatment of erectile dysfunction in hypertensive male cardiac transplant recipients (CTR); however, little is known about the vascular effects of sildenafil in these patients. METHODS: Central and peripheral arterial blood pressure (BP), heart rate, and brachial artery reactivity were determined in 15 hypertensive male CTR before and after oral sildenafil (50 mg) administration. RESULTS: Sildenafil improved brachial and aortic systolic BP, pulse pressure, aortic augmentation index, left ventricular tension time index, travel time of the reflected aortic pressure wave, and brachial artery reactivity (P <.01 for each comparison). No patient became hypotensive with sildenafil despite continuation of usual antihypertensive medications. CONCLUSIONS: Sildenafil (50 mg) is well tolerated in hypertensive CTR and improves BP, aortic augmentation index, and endothelial function. By decreasing the amplitude of the reflected pressure wave and delaying its return to the heart, sildenafil reduces left ventricular afterload and systolic stress.

Aged↗
PubMed2003

Resistance exercise training and alendronate reverse glucocorticoid-induced osteoporosis in heart transplant recipients.

BACKGROUND: Immunosuppression therapy with bolus glucocorticoids causes regional osteoporosis in the axial skeleton of heart transplant recipients (HTR). No preventive strategy is generally accepted for steroid-induced bone loss. METHODS: To determine the efficacy of an anti-osteoporosis regimen that combined a bisphosphonate agent (alendronate sodium) with the osteogenic stimulus of mechanical loading, 25 HTRs were randomly assigned either to a group that received alendronate (10 mg/day) for 6 months (ALEN; n = 8), a group that received alendronate (10 mg/day) and performed specific resistance exercises for 6 months (ALEN + TRN; n = 8) or to a non-intervention control group (CONTR; n = 9). Alendronate was initiated at 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L-2 and L-3) was measured by dual-energy X-ray absorptiometry before and 2, 5 and 8 months after transplantation. Resistance training consisted of lumbar extension exercise (MedX) performed 1 day/week and 8 variable resistance exercises (MedX) performed 2 days/week. RESULTS: Pre-transplantation BMD values did not differ among the 3 groups. BMD of the total body, femur neck and lumbar vertebra were significantly decreased below baseline at 2 months after transplantation in CONTR (-2.6 +/- 0.9%, -5.1 +/- 1.8%, -12.5 +/- 4.2%, respectively), ALEN (-2.8 +/- 0.8%, -5.3 +/- 1.6%, -12.0 +/- 3.9%) and ALEN + TRN groups (-2.7 +/- 1.0%, -5.6 +/- 2.1%, -11.2 +/- 3.7%). CONTR had further significant losses of BMD after 3 and 6 months. ALEN had no further regional BMD losses after initiation of alendronate therapy. ALEN + TRN restored BMD of the whole body, femur neck and lumbar vertebra to within 0.9%, 2.1%, and 3.4% of pre-transplantation levels, respectively. CONCLUSIONS: Resistance exercise plus alendronate was more efficacious than alendronate alone in restoring BMD in HTRs. Our results indicate that anti-osteoporosis therapy in this population should include both an anti-resorptive agent as well as an osteogenic stimulus, such as mechanical loading.

Alendronate↗