cardiovascular-agents and Fatigue

Topics: Adult; Androstenes; Anxiety; Blood Volume; Cardiovascular Agents; Catheter Ablation; Combined Modality Therapy; Confusion; Contraindications; Diagnosis, Differential; Fatigue; Female; Hemodynamics; Humans; Leg; Mast Cells; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Posture; Renin-Angiotensin System; Sodium Chloride; Sympathetic Nervous System; Syncope; Syndrome; Tachycardia

beta-Blocker therapy remains substantially underused in cardiac patients despite its proven mortality benefits. Reluctance to prescribe these agents may derive from concerns about their association with symptoms of depression, fatigue, and sexual dysfunction.. To determine the association of beta-blockers with depressive symptoms, fatigue, and sexual dysfunction by performing a quantitative review of randomized trials that tested beta-blockers in myocardial infarction, heart failure, and hypertension.. Randomized trials of beta-blockers used in the treatment of myocardial infarction, heart failure, or hypertension were identified by searching the MEDLINE database for English-language articles (1966-2001). In addition, we searched the reference lists of previously published trials and reviews of beta-blockers for additional studies.. Criteria for inclusion of trials in the review were: random allocation of study treatments, placebo control, noncrossover design, enrollment of at least 100 patients, and a minimum of 6 months of follow-up. The initial search produced 475 articles, 42 of which met these criteria. Fifteen of these trials reported on depressive symptoms, fatigue, or sexual dysfunction and were selected for inclusion.. For each trial, 1 author abstracted the frequency of adverse events in the beta-blocker and placebo groups and the numbers of patients randomized to the treatment groups. Two other authors verified the counts of events, and all authors adjudicated any discrepancies. Two different types of information on adverse events were abstracted: patient-reported symptoms and withdrawal of therapy due to a specified symptom. We categorized the tested beta-blockers by generation (early vs late) and lipid solubility (high vs low to moderate).. The 15 trials involved more than 35,000 subjects. beta-Blocker therapy was not associated with a significant absolute annual increase in risk of reported depressive symptoms (6 per 1000 patients; 95% confidence interval [CI], -7 to 19). beta-Blockers were associated with a small significant annual increase in risk of reported fatigue (18 per 1000 patients; 95% CI, 5-30), equivalent to 1 additional report of fatigue for every 57 patients treated per year with beta-blockers. beta-Blockers were also associated with a small, significant annual increase in risk of reported sexual dysfunction (5 per 1000 patients; 95% CI, 2-8), equivalent to one additional report for every 199 patients treated per year. None of the risks of adverse effects differed significantly by degree of beta-blocker lipid solubility. The risk associated with reported fatigue was significantly higher for early-generation than for late-generation beta-blockers (P =.04).. The conventional wisdom that beta-blocker therapy is associated with substantial risks of depressive symptoms, fatigue, and sexual dysfunction is not supported by data from clinical trials. There is no significant increased risk of depressive symptoms and only small increased risks of fatigue and sexual dysfunction. The risks of these adverse effects should be put in the context of the documented benefits of these medications.

Topics: Adrenergic beta-Antagonists; Cardiovascular Agents; Depression; Fatigue; Female; Heart Failure; Humans; Hypertension; Male; Myocardial Infarction; Randomized Controlled Trials as Topic; Risk; Sexual Dysfunction, Physiological

Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, leading to chronic disability. Fatigue is a common and distressing symptom of MS which is unrelated to its clinical form, stage of development, the degree of disability, or the lesion load on magnetic resonance imaging. Fatigue in MS is associated with excessive daytime sleepiness and autonomic dysfunction. Recently it has been reported that the wakefulness-promoting drug modafinil may relieve fatigue in MS patients and ameliorate the associated cognitive difficulties. However, it is not clear to what extent the anti-fatigue effect of modafinil may be related to its alerting and sympathetic activating effects. We addressed this question by comparing three groups of subjects, MS patients with fatigue, MS patients without fatigue and healthy controls, matched for age and sex, on measures of alertness (self-ratings on the Epworth and Stanford Sleepiness Scales and on a battery of visual analogue scales; critical flicker fusion frequency; Pupillographic Sleepiness Test; choice reaction time) and autonomic function (systolic and diastolic blood pressure, heart rate, pupil diameter), and by examining the effect of a single dose (200 mg) of modafinil on these measures. MS patients with fatigue, compared with healthy controls, had reduced level of alertness on all the tests used; MS patients without fatigue did not differ from healthy controls. MS patients with fatigue had a reduced level of cardiovascular sympathetic activation compared to the other two groups. Modafinil displayed alerting and sympathomimetic effects in all three groups of subjects. As fatigue in MS is associated with reduced levels of alertness and sympathetic activity, modafinil may exert its anti-fatigue effect in MS by correcting these deficiencies. The anti-fatigue effect of modafinil may reflect the activation of the noradrenergic locus coeruleus (LC), since there is evidence that this wakefulness-promoting nucleus is damaged in MS, and that modafinil, probably via the dopaminergic system, can stimulate the LC. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Topics: Adult; Arousal; Autonomic Nervous System; Benzhydryl Compounds; Cardiovascular Agents; Central Nervous System Stimulants; Cross-Over Studies; Double-Blind Method; Fatigue; Female; Humans; Male; Middle Aged; Modafinil; Multiple Sclerosis; Nootropic Agents; Psychomotor Performance; Sleep Stages; Sleep Wake Disorders; Sympathetic Nervous System; Sympathomimetics

To assess the prevalence of heart failure and asymptomatic left ventricular systolic dysfunction in the chronically paced population.. Three hundred and seven patients were identified from attendance at routine pacemaker follow-up clinic. Subjects underwent a medical history and examination, 6-minute walk test and echocardiography. 94 (31%) had a left ventricular ejection fraction (LVEF) <40%, of whom 83 had symptoms of heart failure (70% NYHA II, 26% NYHA III and 4% NYHA IV). Heart failure was more prevalent in patients with single chamber compared to dual chamber pacemakers, (DDD(R) 18% vs 35% VVI(R), p<0.008), and those with chronic atrial fibrillation (AF) compared to those with sinus rhythm (42% vs 21%, p=0.003). Decreasing 6-minute walk distance, history of ischaemic heart disease and years of pacing were independently associated with the presence of heart failure (combined R=0.572, p<0.001).. Heart failure due to left ventricular systolic dysfunction is common in the paced population. Only a minority of these had a pre-existing diagnosis and a smaller proportion were on 'optimal' therapy. Echocardiographic screening of this high-risk population is justified to improve rates of diagnosis and treatment of heart failure.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Blood Flow Velocity; Cardiac Output, Low; Cardiac Pacing, Artificial; Cardiovascular Agents; Diabetic Angiopathies; Double-Blind Method; Dyspnea; Echocardiography; Exercise Tolerance; Fatigue; Female; Humans; Male; Middle Aged; Risk Factors; Stroke Volume; Ventricular Dysfunction, Left

The renin-angiotensin system plays an important part in the pathogenesis of congestive heart failure (CHF). This study evaluated the effect of an angiotensin II type 1 receptor antagonist on exercise tolerance and symptoms of CHF.. In this multicenter, double-blind, parallel-group study, 844 patients with CHF were randomized to 12 weeks' treatment with placebo (n=211) or candesartan cilexetil 4 mg (n=208), 8 mg (n=212), or 16 mg (n=213) after a 4-week placebo run-in period. Changes in exercise time, Dyspnea Fatigue Index score, NYHA functional class, and cardiothoracic ratio were determined. Candesartan cilexetil produced a dose-related improvement in exercise time. For the intention-to-treat population, the increase produced by candesartan cilexetil 16 mg was significantly greater than that produced by placebo (47.2 versus 30.8 seconds, P=0.0463). All doses of candesartan cilexetil significantly improved the Dyspnea Fatigue Index score relative to placebo. NYHA class improved more frequently in the candesartan cilexetil groups; the differences relative to placebo were not significant. The decrease in cardiothoracic ratio with candesartan 4 to 16 mg was small but statistically significant compared with placebo (all P<0.05). In all candesartan cilexetil groups, plasma renin activity and angiotensin II levels increased from baseline and aldosterone levels decreased in the 8- and 16-mg treatment groups. Candesartan cilexetil was well tolerated at all doses.. In summary, treatment with candesartan cilexetil demonstrated significant improvements in exercise tolerance, cardiothoracic ratio, and symptoms and signs of CHF and was well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II; Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Cardiovascular Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Dyspnea; Exercise Test; Exercise Tolerance; Fatigue; Female; Heart Failure; Humans; Hypotension; Male; Middle Aged; Prospective Studies; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin; Severity of Illness Index; Tetrazoles

Prolonged exercise and exercise training can adversely affect cardiac function in some individuals. QiShenYiQi Pills (QSYQ), which are a compound Chinese medicine, have been previously shown to improve pressure overload-induced cardiac hypertrophy. We hypothesized that QSYQ can ameliorate as well the fatigue-induced cardiac hypertrophy. This study was to test this hypothesis and underlying mechanism with a focus on its role in energy regulation. Male Sprague-Dawley rats were used to establish exercise adaptation and fatigue model on a motorized rodent treadmill. Echocardiographic analysis and heart function test were performed to assess heart systolic function. Food-intake weight/body weight and heart weight/body weight were assessed, and hematoxylin and eosin staining and immunofluorescence staining of myocardium sections were performed. ATP synthase expression and activity and ATP, ADP, and AMP levels were assessed using Western blot and ELISA. Expression of proteins related to energy metabolism and IGF-1R signaling was determined using Western blot. QSYQ attenuated the food-intake weight/body weight decrease, improved myocardial structure and heart function, and restored the expression and distribution of myocardial connexin 43 after fatigue, concomitant with an increased ATP production and a restoration of metabolism-related protein expression. QSYQ upgraded the expression of IGF-1R, P-AMPK/AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, P-phosphatidylinositol 3-kinase (PI3K)/PI3K, and P-Akt/Akt thereby attenuated the dysregulation of IGF-1R signaling after fatigue. QSYQ relieved fatigue-induced cardiac hypertrophy and enhanced heart function, which is correlated with its potential to improve energy metabolism by regulating IGF-1R signaling.

Topics: Adenosine Triphosphate; Animals; Cardiovascular Agents; Cell Line; Disease Models, Animal; Drugs, Chinese Herbal; Energy Metabolism; Fatigue; Hypertrophy, Left Ventricular; Male; Myocytes, Cardiac; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Receptor, IGF Type 1; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling

Patients developing cancer treatment-related left ventricular dysfunction (CTrLVD) require a prompt therapy. Hypotension, dizziness, and fatigue often limit the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and β-blockers (BB) in cancer patients who may already be afflicted by these symptoms. Ivabradine is a heart rate-lowering drug that does not cause hypotension and may be used in heart failure with reduced left ventricular ejection fraction (LVEF).. The aim of this paper was to investigate the role of ivabradine to treat CTrLVD.. A retrospective analysis in a cohort of 30 patients with CTrLVD (LVEF < 50%) receiving ivabradine on top of the maximal tolerated dose of ACEi/ARB and BB was performed. We evaluated cardiovascular treatment, oncologic treatment, LVEF, functional class (New York Heart Association [NYHA]), and fatigue during the study period.. Ivabradine was initially started at the dose of 2.5 mg/b.i.d. in most patients and then carefully titrated. Hypotension (70%) and fatigue (77%) were the main causes limiting the treatment with ACEi/ARB and BB. After a mean follow-up of 6.5 months, LVEF increased from 45.1% (SD = 6.4) to 53.2% (SD = 3.9; p < 0.001). When patients were analyzed according to the type of cancer therapy, no difference in LVEF changes across the groups was found. NYHA class ameliorated in 11 patients, while fatigue improved in 8 patients. No serious cardiovascular side effects were reported.. The ability to improve symptoms and LVEF in unfit cancer patients makes ivabradine a reasonable pharmacological tool for treating CTrLVD.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Cardiovascular Agents; Dose-Response Relationship, Drug; Fatigue; Female; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Neoplasms; Retrospective Studies; Trastuzumab; Ventricular Dysfunction, Left

Patient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process.. Concept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items.. During concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders.. Development of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program.

Topics: Aged; Aged, 80 and over; Cardiac Myosins; Cardiovascular Agents; Clinical Trials as Topic; Dizziness; Dyspnea; Edema; Fatigue; Female; Focus Groups; Heart Failure; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Qualitative Research; Quality of Life; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration; Urea

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Digoxin; Drug-Eluting Stents; Fatigue; Humans; Male; Physician-Patient Relations

The study aimed to compare the clinical picture and treatment differences in elderly patients (aged 75 years or older) and younger patients (aged below 75 years).. The study included 80 consecutive patients with myocardial infarction (MI) treated in the Cardiology Ward of the Specialist Hospital in Radom, Poland, in 2005. Analyses were performed retrospectively. The patients were separated into 2 groups according to age. The group I study group consisted of 40 patients aged 75 or over (aged 75-95; mean 81 years) and the group II control group consisted of 40 patients aged below 75 years (aged 42-67; mean 60 years).. In the elderly, as compared with younger subjects, dyspnea, fatigue, and other heart failure symptoms, were more frequently the first symptoms of MI than typical chest pain (p<0.05). ST-segment elevation myocardial infarction (STEMI) was also more common (p<0.05). Non-ST-segment elevation myocardial infarction (NSTEMI) was more frequently diagnosed in the elderly (p<0.05). In elderly patients there were more women (p<0.05), more patients with previously diagnosed ischemic heart disease (p<0.05), with hypertension (p<0.05), and with diabetes mellitus (p<0.05). Obesity was less frequently diagnosed in the elderly; however the difference was not statistically significant. Dyslipidemia and cigarette smoking were both significantly less common among elderly patients (p<0.05). The elderly were significantly less frequently revascularized (p<0.05). Both fibrinolysis and primary percutaneous coronary intervention (PCI) were less commonly applied to the elderly (p<0.05). Time from symptom onset to hospital admission was significantly longer in the case of elderly patients (p<0.05). The MI complications and side effects of treatment seemed to be more frequent in the elderly, but only post-MI heart failure was observed more frequently in this group of patients (p<0.05).. Our observations confirm the differences in the clinical picture of MI in the elderly as described previously. All patients of advanced age should be considered as having the highest risk of death and complications occurrence.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Bypass; Dyspnea; Fatigue; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Poland; Retrospective Studies; Risk Assessment; Risk Factors; Thrombolytic Therapy; Time Factors; Treatment Outcome

We sought to determine whether poorer outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (MI) during off-hours are related to delays in treatment, circadian changes in biology, or differences in operator-related quality of care.. Previous investigation has suggested that patients undergoing primary PCI during off-hours are more likely to have adverse cardiac events than routine-hours patients, but the reasons for this remain poorly defined.. Clinical, angiographic, and procedural characteristics were compared in consecutive patients (n = 685) undergoing primary PCI in the National Heart, Lung, and Blood Institute Dynamic Registry between 1997 and 2006 that were classified as occurring during routine-hours (07:00 to 18:59) or off-hours (19:00 to 06:59). The primary end points were in-hospital death, MI, and target vessel revascularization.. Median time from symptom onset to PCI was similar (off-hours 3.4 h vs. routine-hours 3.3 h). Patients presenting in off-hours were more likely to present with cardiogenic shock and multivessel coronary artery disease but were equally likely to present with complete occlusion of the infarct-related artery. Procedural complications including dissection were more frequent in off-hours patients. In-hospital death, MI, and target vessel revascularization were significantly higher in off-hours patients (adjusted odds ratio [OR]: 2.66, p = 0.001), and differences in outcomes were worse even if the procedure was immediately successful (adjusted OR: 2.58, p = 0.005, adjusting for angiographic success). Patients undergoing PCI on weekends had better outcomes during the daytime than nighttime.. Patients undergoing primary PCI for acute MI during off-hours are at significantly higher risk for in-hospital death, MI, and target vessel revascularization. These findings appear related to both diurnal differences in presentation and lesion characteristics, as well as differences in procedural complication and success rates that extend beyond differences in symptom-to-balloon time.

Topics: After-Hours Care; Aged; Angioplasty, Balloon, Coronary; Attitude of Health Personnel; Cardiovascular Agents; Circadian Rhythm; Clinical Competence; Coronary Angiography; Fatigue; Female; Guideline Adherence; Health Knowledge, Attitudes, Practice; Health Services Accessibility; Hospital Mortality; Humans; Male; Medical Errors; Middle Aged; Myocardial Infarction; Odds Ratio; Outcome and Process Assessment, Health Care; Personnel Staffing and Scheduling; Practice Guidelines as Topic; Recurrence; Registries; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States; Workload