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Biomedical subjects

Richard S Schofield

Publications and source records attributed to Richard S Schofield.

35 records · Page 2Linked to original sources
PubMed2004

Effect of exercise training on central aortic pressure wave reflection in coronary artery disease.

BACKGROUND: Arterial stiffness is an important factor for cardiovascular performance and a predictor of cardiovascular risk. We investigated the effect of exercise training on arterial stiffness in coronary artery disease (CAD). METHODS: Arterial stiffness was assessed before and after 12 weeks of either exercise training or standard care in CAD patients. Arterial stiffness was evaluated by aortic augmentation index and time delay of the reflected wave (Deltat) using the SphygmoCor system. RESULTS: The augmentation index decreased (30% v 26%, P <.05) and Deltat increased (136 msec v 144 msec, P <.05) in patients with CAD after 12 weeks of exercise. CONCLUSION: These results suggest that endurance exercise training improves systemic arterial stiffness in individuals with CAD.

Aged↗
PubMed2004

Left ventricular dysfunction after pericardiectomy for constrictive pericarditis.

A 56-year-old man was admitted to our hospital with a diagnosis of suspected constrictive pericarditis. After the diagnosis was confirmed by cardiac catheterization, an elective pericardiectomy was performed without complication. Four days after surgery dyspnea developed in the patient, and he was found to have an acute decrease in left ventricular ejection fraction (LVEF) by echocardiography. The patient's symptoms and the LVEF improved over time and returned to normal 4 weeks after surgery. Transient hemodynamic dysfunction of the left ventricle has previously been reported after pericardiectomy or pericardiocentesis; however, we know of no reports in the literature that confirm an acute reduction in LVEF by echocardiography after pericardiectomy for constrictive pericarditis.

Echocardiography↗
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

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

Comparison of dobutamine versus milrinone therapy in hospitalized patients awaiting cardiac transplantation: a prospective, randomized trial.

BACKGROUND: The use of dobutamine or milrinone for inotropic support in patients with heart failure awaiting cardiac transplantation is largely arbitrary and based on institutional preference. The costs and effectiveness of these drugs have yet to be compared in a prospective, randomized study. METHODS: We compared clinical outcomes and costs associated with the use of dobutamine or milrinone in 36 hospitalized patients awaiting cardiac transplantation. Patients were randomly assigned to receive either dobutamine or milrinone at the time of initial hospitalization and were followed until death, transplantation, or placement of mechanical cardiac support (intra-aortic balloon pump or left ventricular assist device). RESULTS: Seventeen patients were randomly assigned to receive dobutamine (mean dose 4.1 +/- 1.4 microg/kg/min) and 19 patients received milrinone (mean dose 0.39 +/- 1.0 microg/kg/min). Therapy lasted 50 +/- 46 days for those in the dobutamine group and 63 +/- 45 days in the milrinone group. We did not detect differences between the 2 groups in right heart hemodynamics, death, need for additional vasodilator/inotropic therapy, or need for mechanical cardiac support before transplantation. Ventricular arrhythmias requiring increased antiarrhythmic therapy occurred frequently in both groups. Total acquisition cost of milrinone was significantly higher than that of dobutamine (16,270 dollars +/- 1334 vs 380 dollars +/- 533 P <.00001). CONCLUSIONS: Both dobutamine and milrinone can be used successfully as pharmacologic therapy for a bridge to heart transplantation. Despite similar clinical outcomes, treatment with milrinone incurs greater cost.

Adrenergic beta-Agonists↗
PubMed2003

The evolving role of nesiritide in advanced or decompensated heart failure.

Nesiritide is a recombinant form of human brain natriuretic peptide (BNP) that is structurally and biochemically identical to endogenously produced BNP. In humans, BNP is important in hemodynamic and neurohormonal equilibrium, helping to maintain adequate vascular volume and pressure in response to volume overload. The pharmacodynamic effects of nesiritide mimic the biologic effects of BNP. The molecular biology and actions of nesiritide and BNP are reviewed, with the therapeutic rationale for nesiritide in patients with acute or advanced decompensated heart failure highlighted. In addition, recommendations for its administration are provided, and unresolved therapeutic considerations are discussed.

Heart Failure↗
PubMed2003

Pharmacological treatment of patients with peripheral arterial disease.

Atherosclerosis is a disease process that affects the coronary, cerebral and peripheral arterial circulation. While great emphasis has been placed on the aggressive pharmacological management of coronary artery disease, less attention has been paid to the pharmacological management of peripheral vascular disease, despite its significant morbidity and mortality. The purpose of medical management in peripheral arterial disease is to relieve symptoms of claudication and to prevent thrombotic vascular events. These goals are best achieved through aggressive risk factor modification and pharmacotherapy. Risk factor modification includes smoking cessation, adequate control of blood pressure and cholesterol, as well as aggressive glycaemic control in patients with diabetes mellitus. Antiplatelet therapy and relief of claudication is also achieved through pharmacotherapy. With aggressive risk factor modification and adequate pharmacotherapy, patients with peripheral arterial disease can have an improved quality of life as well as prolonged survival.

Arteriosclerosis↗
PubMed2002

Electroluminescent zinc(II) bis(8-hydroxyquinoline): structural effects on electronic states and device performance.

We present direct evidence for stable oligomers in vacuum-deposited thin films of zinc(II) bis(8-hydroxyquinoline) (Znq(2)). The tetramer [(Znq(2))(4)] is the energetically favored configuration in both the single crystal and the vacuum-deposited thin film. Oligomerization leads to distinct, symmetry-driven differences between the electronic states in Znq(2) and those in the archetypal organic electroluminescent molecule tris(8-hydroxyquinoline) aluminum (Alq(3)). In the case of the Znq(2) tetramer, symmetry leads to an extended network of overlapping pyridyl and phenolato moieties in the solid film. Analysis of the electronic structure of (Znq(2))(4) calculated by ab initio Hartree-Fock (HF) methods reveals a localization and energy shift of high-lying occupied and low-lying unoccupied states on symmetry related ligands located on opposite sides of the supramolecular structure resulting in a dipole moment for (Znq(2))(4) tetramer close to zero. The optimal pi-overlap pathways, altered charge distributions, and extended electronic states of tetrameric Znq(2) may be expected to enable low operating voltage organic light-emitting devices (OLEDs) based on Znq(2). We present preliminary evidence that the operating voltage of (Znq(2))(4)-based OLEDs is indeed lower than that of identical devices made with Alq(3). Strategic substitution of 8-hydroxyquinoline ligands and control of the structural symmetry of the corresponding metal chelates may offer a route to high efficiency and low operating voltage small molecule OLEDs.

Journal Article↗
PubMed2002

Anti-CD20 monoclonal antibody (rituximab) therapy for acute cardiac humoral rejection: a case report.

Humoral or antibody-mediated rejection in cardiac transplant recipients is mediated by donor-specific cytotoxic antibodies and is histologically defined by linear deposits of immunoglobulin and complement in the myocardial capillaries. Antibody-mediated rejection often is accompanied by hemodynamic compromise and is associated with reduced long-term graft survival. Standard immunosuppression, designed to target T cell immune function, is largely ineffective against this B cell-driven process. Current treatment options for humoral rejection are limited by a lack of specific anti-B cell therapies. We present the case of a 50-year-old woman with hemodynamically significant humoral rejection resistant to steroids, cyclophos-phamide, and plasmapheresis who responded to the addition of anti-CD20 monoclonal antibody therapy (rituximab). One year posttransplant, the patient is rejection-free, with normal left ventricular systolic function and coronary arteries.

Acute Disease↗
PubMed2002

Ventricular dyssynchrony in dilated cardiomyopathy: the role of biventricular pacing in the treatment of congestive heart failure.

Despite advances in pharmacologic therapy, the prognosis of patients with advanced congestive heart failure (CHF) remains poor. Many of these patients have cardiac conduction abnormalities, such as left bundle-branch block or interventricular conduction delays, that can lead to ventricular dyssynchrony (abnormal ventricular activation that results in decreased ventricular filling and abnormal ventricular wall motion). Biventricular pacing is an alternative, nonpharmacologic therapy under active investigation for the treatment of CHF. Resynchronization devices with transvenous leads in the right atrium, right ventricle, and left ventricle (via the coronary sinus) have been implanted in patients to provide atrial triggered biventricular pacing. The use of such devices has been associated with improvement in ejection fraction, dP/dt, stroke work, and functional class. The proposed mechanisms involved in improving ventricular function with biventricular pacing include improved septal contribution to ventricular ejection, increased diastolic filling times, and reduced mitral regurgitation. This article reviews the pathophysiology of ventricular dyssynchrony and examine insights from clinical trials that are evaluating cardiac resynchronization therapy for CHF.

Cardiac Pacing, Artificial↗
PubMed2002

Amplitude and timing of central aortic pressure wave reflections in heart transplant recipients.

BACKGROUND: Hypertension (HTN) assessed by sphygmomanometer is a common finding in heart transplant recipients (HTR); however, little is known about the contribution of arterial wave reflection to central aortic pressure in these patients. The aim of this study was to measure the central aortic pressure wave in HTR on antihypertensive therapy and determine the effects of amplitude and timing of wave reflection on the various components of the wave. METHODS: A total of 53 stable adult HTR on antihypertensive medication underwent brachial artery blood pressure ([BP]; by sphygmomanometry) and central aortic pressure (by noninvasive radial artery applanation tonometry and use of a generalized transfer function) measurements at rest. Central aortic augmentation index (Ala), an indicator of arterial stiffness, was calculated from the aortic pressure waveform. Patients were divided into three groups (A, B, and C) based on the amplitude of AIa. RESULTS: Mean brachial BP was 136 +/- 15/84 +/- 9.4 mm Hg. Group A patients (n = 25) had a higher AIa (average 21% +/- 7.6%) than group B (n = 18, AIa = 6.5% +/- 3.0%, P < .001) or group C (n = 10, AIa = -8.7% +/- 8.1%, P < .001) patients. The amplitude of AIa was inversely related to the travel time (delta(t)p/2) of the reflected pressure wave from the periphery to the heart (r = -0.78, P < .001). Despite this clear stratification of patients by aortic pulse wave analysis, standard cuff pressure was similar among the groups. CONCLUSIONS: Noninvasive analysis of the central aortic PRESSURE wave identified a subgroup of hypertensive HTR with increased arterial stiffness, increased propagation of the reflected wave, and augmented aortic systolic and pulse pressure not identified with the sphygmomanometer.

Adult↗
PubMed2002

Hormone therapy in men and risk of cardiac allograft rejection.

Hormone therapy with leuprolide acetate (Lupron) is frequently used to treat prostate cancer, a common malignancy expected to be diagnosed in >180,000 men in the United States this year. In addition, testosterone supplementation is frequently recommended for adult men with reduced libido or impotence and decreased serum levels of testosterone. Although these hormone therapies are generally considered benign, we describe 3 cases of acute cardiac rejection temporally associated with the use of these drugs in men who have undergone cardiac transplantation. To our knowledge, this is the first such description of this phenomenon in the literature.

Acute Disease↗
PubMed2002

Percutaneous coronary intervention versus medical therapy for coronary allograft vasculopathy. One center's experience.

BACKGROUND: Coronary allograft vasculopathy, a rapidly progressive form of atherosclerosis, remains the limiting factor in the long-term survival of heart transplant recipients. Some centers have attempted percutaneous coronary intervention to slow the disease process and thereby reduce mortality in these patients, but long-term follow-up data are scarce. We compared clinical outcomes in heart transplant recipients with coronary allograft vasculopathy who were treated either with percutaneous coronary intervention or with aggressive medical therapy alone. METHODS: A retrospective analysis of all heart transplant recipients at our institution who underwent surveillance coronary angiography for coronary allograft vasculopathy between 1995 and 2000 was performed. Patients with coronary allograft vasculopathy were stratified according to whether they received medical therapy or percutaneous coronary intervention. Baseline demographics, results of re-vascularization procedures and outcomes were analyzed. RESULTS: From 1995 to 2000, 301 patients underwent 602 coronary angiograms. Of the 79 patients who had angiographic evidence of coronary allograft vasculopathy, 53 were treated with aggressive medical therapy, while 26 underwent percutaneous coronary intervention in addition to aggressive medical therapy. At baseline, patients treated with aggressive medical therapy tended to be younger (54.6 +/- 13.8 years) than patients treated with percutaneous coronary intervention (62.6 +/- 7.6 years; p = 0.0079). Ejection fraction at time of diagnosis of coronary allograft vasculopathy was similar for both groups (medical therapy group, 44.4 +/- 13.4% vs percutaneous coronary intervention group, 47.2 +/- 12.7%; p = 0.38). In our cohort, heart transplant recipients with coronary allograft vasculopathy demonstrated greater mortality than heart transplant recipients without coronary allograft vasculopathy (p = 0.016). Patients who underwent percutaneous coronary intervention had a 60% re-stenosis rate at 6 months if they were treated with coronary angioplasty and an 18% re-stenosis rate if they received a coronary stent. Kaplan-Meier analysis showed no significant difference in survival in either treatment group at 1 year (80% for medical therapy group vs 95% for percutaneous coronary intervention group) or 3 years (68% for medical therapy group vs 79% for percutaneous coronary intervention group) after the angiographic diagnosis of coronary allograft vasculopathy. CONCLUSION: In this non-randomized trial, heart transplant recipients with coronary allograft vasculopathy were less likely to survive than patients without it. In addition, we found no statistical difference in mortality in heart transplant recipients with coronary allograft vasculopathy, regardless of whether they received percutaneous coronary intervention or aggressive medical therapy alone.

Aged↗
PubMed2002

The use of ranolazine in cardiovascular disease.

Ranolazine is a novel drug that has shown promise in the treatment of cardiovascular disease. Ranolazine exerts its effect by shifting myocardial energy metabolism away from free fatty acids and toward glucose as the substrate for production of adenosine triphosphate. Preclinical data have confirmed that ranolazine reduces myocardial ischaemic injury in various animal models. Researchers are continuing to gather clinical data but findings to date support the conclusion that ranolazine has anti-ischaemic effects without inducing the typical reduction in blood pressure and heart rate associated with the use of traditional anti-ischaemic agents. Given the absence of haemodynamic effects associated with ranolazine, it has great promise as a drug that could be added to existing therapy without concern for hypotensive or bradycardic side effects. Ranolazine has been shown to improve exercise-induced myocardial ischaemia and to lessen the severity of angina in the setting of chronic ischaemic heart disease. Early preclinical observations also suggest positive effects of ranolazine in the management of congestive heart failure; however, trials in this area are ongoing. Several recently completed Phase III clinical studies in patients with chronic ischaemic heart disease have confirmed the findings of smaller trials and should satisfy regulatory concerns necessary to place ranolazine on the commercial market in the US. The maker of ranolazine, CV Therapeutics (Palo Alto, California), will file a New Drug Application (NDA) with the US FDA for the approval of ranolazine as an anti-anginal in the near future.

Acetanilides↗
PubMedDate not supplied

Managing the post-left ventricular assist device patient.

The implantation of ventricular assist devices allows the opportunity for patients with intractable heart failure to have improved quality and quantity of life. The devices may be implanted after failed attempts to wean from bypass, as a bridge to transplantation, or as destination therapy. Key issues following the implantation of assist devices include the prevention of right ventricular failure, appropriate pharmacologic management, prevention and management of infection, and detection and treatment of device dysfunction.

Assisted Circulation↗