Background: The cholinesterase inhibitor pyridostigmine is used to treat orthostatic hypotension by facilitating cholinergic neurotransmission in autonomic ganglia, thereby harnessing residual sympathetic tone to increase blood pressure (BP) preferentially in the upright posture. We hypothesized that less severe autonomic impairment was associated with greater pressor responses to pyridostigmine.
Methods: To identify predictors of pressor response, linear regression analyses between the effect of pyridostigmine on upright BP and markers of autonomic impairment were retrospectively conducted on 38 patients who had a medication trial with pyridostigmine (60 mg single dose).
Circ Arrhythm Electrophysiol
September 2022
Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms.
View Article and Find Full Text PDFCirc Arrhythm Electrophysiol
March 2022
Orthostatic hypotension (OH), a common, often overlooked, disorder with many causes, is associated with debilitating symptoms, falls, syncope, cognitive impairment, and risk of death. Chronic OH, a cardinal sign of autonomic dysfunction, increases with advancing age and is commonly associated with neurodegenerative and autoimmune diseases, diabetes, hypertension, heart failure, and kidney failure. Management typically involves a multidisciplinary, patient-centered, approach to arrive at an appropriate underlying diagnosis that is causing OH, treating accompanying conditions, and providing individually tailored pharmacological and nonpharmacological treatment.
View Article and Find Full Text PDFOrthostatic hypotension is a frequent cause of falls and syncope, impairing quality of life. It is an independent risk factor of mortality and a common cause of hospitalizations, which exponentially increases in the geriatric population. We present a management plan based on a systematic literature review and understanding of the underlying pathophysiology and relevant clinical pharmacology.
View Article and Find Full Text PDFBackground: Evidence supports scheduling early follow-up after heart failure (HF) hospitalization with a provider capable of managing hypervolemia. Often this service is provided by cardiologists or specialty nurse practitioners. Continuity or "familiar" providers may be better positioned to identify decompensating HF in patients who have advanced HF and/or multiple complicating medical problems.
View Article and Find Full Text PDFBackground Supine hypertension affects a majority of patients with autonomic failure; it is associated with end-organ damage and can worsen daytime orthostatic hypotension by inducing pressure diuresis and volume loss during the night. Because sympathetic activation prevents blood pressure (BP) from falling in healthy subjects exposed to heat, we hypothesized that passive heat had a BP-lowering effect in patients with autonomic failure and could be used to treat their supine hypertension. Methods and Results In Protocol 1 (n=22), the acute effects of local heat (40-42°C applied with a heating pad placed over the abdomen for 2 hours) versus sham control were assessed in a randomized crossover fashion.
View Article and Find Full Text PDFAuton Neurosci
September 2020
Neurogenic orthostatic hypotension (nOH) is a common comorbidity in patients with neurodegenerative diseases. It is associated with an increased risk of falls, incident cardiovascular disease, and all-cause mortality. There are over 5 million individuals in the U.
View Article and Find Full Text PDFAlthough diagnostic criteria have been developed characterizing postural orthostatic tachycardia syndrome (POTS), no single set of criteria is universally accepted. Furthermore, there are gaps in the present criteria used to identify individuals who have this condition. The reproducibility of the physiological findings, the relationship of symptoms to physiological findings, the presence of symptoms alone without any physiological findings and the response to various interventions confuse rather than clarify this condition.
View Article and Find Full Text PDFNeurogenic orthostatic hypotension (nOH), a drop in blood pressure upon standing resulting from autonomic malfunction, may cause debilitating symptoms that can affect independence in daily activities and quality-of-life. nOH may also be associated with cardiovascular comorbidities (e.g.
View Article and Find Full Text PDFAfferent baroreflex failure is most often due to damage of the carotid sinus nerve because of neck surgery or radiation. The clinical picture is characterized by extreme blood pressure lability with severe hypertensive crises, hypotensive episodes, and orthostatic hypotension, making it the most difficult form of hypertension to manage. There is little evidence-based data to guide treatment.
View Article and Find Full Text PDFBackground: Aerobic exercise training is known to have beneficial effects on whole-body glucose metabolism in people with type 2 diabetes (T2D). The responses of the liver to such training are less well understood. The purpose of this study was to determine the effect of aerobic exercise training on splanchnic glucose uptake (SGU) and insulin-mediated suppression of endogenous glucose production (EGP) in obese subjects with T2D.
View Article and Find Full Text PDFA first-in-human, phase 1, double blind, placebo-controlled, single ascending dose study examined the safety, tolerability, and exploratory efficacy of intravenous infusion of a recombinant growth factor, cimaglermin alfa, in patients with heart failure and left ventricular systolic dysfunction (LVSD). In these patients on optimal guideline-directed medical therapy, cimaglermin treatment was generally tolerated except for transient nausea and headache and a dose-limiting toxicity was noted at the highest planned dose. There was a dose-dependent improvement in left ventricular ejection fraction lasting 90 days following infusion.
View Article and Find Full Text PDFBackground And Objectives: Dosing algorithms for warfarin incorporate clinical and genetic factors but may not account for the numerous comorbidities affecting patients who start warfarin while hospitalized. We aimed to determine whether these algorithms perform differently when warfarin is initiated for inpatients compared with outpatients.
Patients And Methods: We analyzed a prospective cohort of 1015 participants from the Clarification of Optimal Anticoagulation through Genetics (COAG) trial who were randomized to either pharmacogenetically or clinically guided warfarin dosing algorithms.
Objective: Inflammation, insulin resistance and vascular dysfunction characterize obesity and predict development of cardiovascular disease (CVD). Although women experience CVD events at an older age, vascular dysfunction is evident 10years prior to coronary artery disease. Questions remain whether replacing SFA entirely with MUFA or PUFA is the optimal approach for cardiometabolic benefits.
View Article and Find Full Text PDFStudy Objectives: Obstructive sleep apnea (OSA) is strongly associated with cardiovascular disease, including stroke and acute coronary syndromes. Plasminogen activator inhibitor-1 (PAI-1), the principal inhibitor of tissue-type plasminogen activator (t-PA), has a pronounced circadian rhythm and is elevated in both OSA and cardiovascular disease and may be an important link between the two conditions. Endothelial dysfunction is one of the underlying pathophysiological mechanisms of cardiovascular disease, and may be altered in OSA.
View Article and Find Full Text PDFBackground: The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.
Methods: We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy.
Expert Opin Drug Metab Toxicol
November 2012
Introduction: The most common risk factors for heart failure are hypertension and myocardial infarction. Angiotensin receptor blockers (ARBs) attenuate the deleterious effects of angiotensin II. Valsartan is a once or twice daily ARB that is FDA-approved for hypertension, LV dysfunction post-myocardial infarction and congestive heart failure as both an adjunct in ACE-inhibitor tolerant, and alternative in ACE-I intolerant patients.
View Article and Find Full Text PDFPlasminogen activator inhibitor 1 (PAI-1), the primary inhibitor of fibrinolysis and C-reactive protein (CRP), is a predictor of myocardial infarction. Both are upregulated by tumor necrosis factor-alpha (TNF-α) within the obese population. This pilot study tested the hypothesis that TNF-α blockade with pentoxifylline lowers PAI-1 and high-sensitivity CRP (hsCRP) in obese individuals.
View Article and Find Full Text PDFEplerenone is an aldosterone receptor antagonist indicated for the treatment of hypertension and congestive heart failure. Eplerenone contains an epoxy group, which offers greater mineralocorticoid receptor specificity. It is an effective antihypertensive that has been shown to reduce morbidity and mortality in individuals with left ventricular dysfunction post myocardial infarction.
View Article and Find Full Text PDFThe acute physiologic release of tissue-type plasminogen activator (t-PA) from the endothelium is critical for vascular homeostasis. This process is prostacyclin- and nitric oxide (NO)-independent in humans. It has been suggested that calcium signaling and endothelial-derived hyperpolarizing factors (EDHF) may play a role in t-PA release.
View Article and Find Full Text PDFObjective: Drug eluting stents (DES) reduce the incidence of restenosis after coronary angioplasty. Enthusiasm has been tempered by a possible increased risk of in-stent thrombosis. We examined the effects of paclitaxel and rapamycin on the endothelial transcriptome to identify alterations in gene expression associated with thrombosis.
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