Detection of elevated right atrial pressure using a simple bedside ultrasound measure.

AIMS: Accurate assessment of right atrial pressure (RAP) often requires invasive measurement. With normal RAP, Valsalva increases right internal jugular vein (RIJV) cross sectional area (CSA) 20% to 30%. With high RAP, when venous compliance is low, we hypothesized that the increase in CSA would be blunted and could be detected non-invasively with bedside ultrasound. METHODS AND RESULTS: RIJV ultrasound images were obtained in 67 patients undergoing right heart catheterization. The median RAP at end-expiration was 7 mm Hg (interquartile range [IQR] 5-9 mm Hg) in patients with normal RAP (n = 47) versus 15 mm Hg (IQR 12-22 mm Hg) in patients with elevated RAP (n = 20). With Valsalva, the median percent change in RIJV CSA was 35% (IQR 19%-79%) versus 5% (IQR 3%-14%) for normal and high RAP, respectively. By receiver operating curve analysis, a <17% increase in RIJV CSA with Valsalva predicted elevated RAP (> or =12 mmHg) with 90% sensitivity, 74% specificity, 94% negative predictive value, and 60% positive predictive value (area under the curve 0.86, P < .001). CONCLUSIONS: An increase in RIJV CSA >17% during Valsalva effectively rules out elevated RAP. This simple bedside technique may be useful to assess central venous pressure and reduce the need for invasive pressure measurement.

Off-label use of stents: bare-metal versus drug-eluting stents.

Drug-eluting stents (DES) became the default strategy for percutaneous revascularization due to their improved intermediate-term outcomes when compared with bare-metal stents (BMS) in the pivotal randomized, controlled trials. The excellent results of DES in on-label or US FDA-approved indications led to extrapolation of the results to more complex situations that were excluded from initial pivotal trials; such as off-label indications. Safety concerns began to grow after reports of increased late thrombosis and possibly associated increased death and myocardial infarction with DES, especially in the off-label situations. Recently, however, several important published registries have calmed some of those uncertainties and reassured the cardiology community of the safety and efficacy of DES compared with BMS. There is an overall poorer outcome with off-label use of any stent (BMS or DES) compared with standard or on-label use. This difference in outcome is most likely related to patient or specific coronary lesion characteristics or comorbidities that predispose an individual to adverse outcomes regardless of the stent type used. It is accepted now that DES use does result in a small increased risk of late thrombosis, but that risk is offset by a significant reduction in restenosis. Overall, the current data suggest that the use of DES in most lesion subsets is at least as safe as and clearly more efficacious than use of BMS in similar situations.

Pulmonary vein thrombosis in the setting of blunt chest trauma.

Pulmonary vein thrombosis has been associated with lung transplantation and lung resection. We report a case of right lower pulmonary vein thrombosis after blunt chest trauma.

Role of metabolically active hormones in the insulin resistance associated with short-term glucocorticoid treatment.

BACKGROUND: The mechanisms by which glucocorticoid therapy promotes obesity and insulin resistance are incompletely characterized. Modulations of the metabolically active hormones, tumour necrosis factor alpha (TNF alpha), ghrelin, leptin and adiponectin are all implicated in the development of these cardiovascular risk factors. Little is known about the effects of short-term glucocorticoid treatment on levels of these hormones. RESEARCH METHODS AND PROCEDURES: Using a blinded, placebo-controlled approach, we randomised 25 healthy men (mean (SD) age: 24.2 (5.4) years) to 5 days of treatment with either placebo or oral dexamethasone 3 mg twice daily. Fasting plasma TNFalpha, ghrelin, leptin and adiponectin were measured before and after treatment. RESULTS: Mean changes in all hormones were no different between treatment arms, despite dexamethasone-related increases in body weight, blood pressure, HDL cholesterol and insulin. Changes in calculated indices of insulin sensitivity (HOMA-S, insulin sensitivity index) were strongly related to dexamethasone treatment (p < 0.001). DISCUSSION: Our data do not support a role for TNF alpha, ghrelin, leptin or adiponectin in the insulin resistance associated with short-term glucocorticoid treatment.

Effects of short-term glucocorticoids on hemostatic factors in healthy volunteers.

OBJECTIVE: Increased circulating levels of hemostatic factors have been associated with arterial and venous thrombosis. Although in vitro evidence suggests that glucocorticoids may activate hemostasis and inhibit thrombolysis, no controlled in vivo studies have examined the effects of glucocorticoids on hemostatic factors. We hypothesized that a 5-day treatment course of dexamethasone would increase circulating levels of hemostatic and anti-fibrinolytic factors. METHODS: We randomized 24 healthy men ages 19-39 to receive either dexamethasone 3 mg twice daily versus placebo for 5 days. Parameters examined before and after the intervention included: clotting factors VII, VIII, and XI, von Willebrand factor (vWF), D-dimer, PAI-1, soluble CD40-ligand (sCD40-ligand), and fibrinogen. RESULTS: Dexamethasone tended to modestly increase clotting factors levels and fibrinogen without significantly affecting PAI-1, D-dimer or sCD40-ligand. Factor VII increased by a mean of 13% (p = 0.04 versus placebo), factor VIII by 27% (p = 0.0008), factor XI by 6% (p = 0.01), and fibrinogen by 13% (p = 0.05). CONCLUSIONS: Glucocorticoids may increase the activity of clotting factors in vivo. This may contribute to the reported increased risk of thrombosis in patients with sustained exposure to glucocorticoids.

Relation of brachial artery reactivity to nitroglycerin and heart rate recovery following exercise in healthy male volunteers.

The parasympathetic nervous system facilitates peripheral arterial vasodilation and is also responsible for a decrease in heart rate immediately after exercise (heart rate recovery [HRR]). The relation among parasympathetic tone measured by HRR after exercise, endothelium-mediated vasodilation, and nitroglycerin-mediated vasodilation (determined with brachial artery ultrasound) was assessed in 25 healthy young men. One-minute HRR was nonsignificantly related to endothelium-mediated vasodilation (r = -0.35, p = 0.08) but was significantly related to nitroglycerin-mediated vasodilation (r = -0.63, p = 0.0008), a finding that persisted after adjustment for heart rate at rest, insulin resistance, lipid variables, and blood pressure. This suggests that parasympathetic tone may be inversely related to the responsiveness of arterial smooth muscle to nitrates in healthy humans.

Effects of short-term glucocorticoids on cardiovascular biomarkers.

CONTEXT: Glucocorticoids are known to acutely increase blood pressure, suppress inflammation, and precipitate insulin resistance. However, the short-term effects of glucocorticoids on other cardiovascular risk factors remain incompletely characterized. OBJECTIVE: Our objective was to determine the effects of a short course of dexamethasone on multiple cardiovascular biomarkers and to determine whether suppression of morning cortisol in response to low-dose dexamethasone is correlated with cardiovascular risk markers in healthy volunteers. DESIGN: We conducted a randomized, double-blind, placebo-controlled study. SETTING: The study took place in a tertiary care hospital. STUDY SUBJECTS: Twenty-five healthy male volunteers, ages 19-39 yr, participated in the study. INTERVENTION: Subjects received either 3 mg dexamethasone twice daily or placebo for 5 d. Subjects also underwent a low-dose (0.5 mg) overnight dexamethasone suppression test. MEASURES: Parameters examined before and after the 5-d intervention included heart rate, blood pressure, weight, fasting lipid variables, homocysteine, renin, aldosterone, insulin resistance (homeostasis model assessment), high-sensitivity C-reactive protein, B-type natriuretic peptide, flow-mediated and nitroglycerin-mediated brachial artery dilatation, and heart rate recovery after exercise. All measurements were done in the morning hours in the fasting state. RESULTS: Dexamethasone increased systolic blood pressure, weight, B-type natriuretic peptide, and high-density-lipoprotein-cholesterol. Dexamethasone decreased resting heart rate, high-sensitivity C-reactive protein, and aldosterone and tended to attenuate nitroglycerin-mediated vasodilatation. There was no effect on flow-mediated vasodilatation, diastolic blood pressure, triglycerides, low-density-lipoprotein-cholesterol, nonesterified fatty acids, homocysteine, or heart rate recovery. The response of circulating cortisol to low-dose dexamethasone had no significant correlation with any of the cardiovascular risk markers. CONCLUSIONS: Short-term glucocorticoids elicits both favorable and unfavorable effects on different cardiovascular risk factors. Manipulation of specific glucocorticoid-responsive physiological pathways deserves further study.

Does altered glucocorticoid homeostasis increase cardiovascular risk?

The hypothalamic-pituitary-adrenal (HPA) axis, like the sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system, sustains life in stressful situations by increasing vascular tone and ensuring fuel availability. It also modulates inflammation and tissue repair processes. Untoward cardiovascular effects of chronic sympathetic and RAA activation are well recognized, illustrating that the short-term benefit of the physiologic stress response can be detrimental in the long term. Similarly, chronic tissue exposure to glucocorticoids may lead to metabolic and vascular changes that accelerate vascular senescence. Specific situations associated with chronic activation of the HPA axis-such as major depression, inflammatory disease and perhaps the metabolic syndrome-may derive some of their associated cardiovascular risk from untoward glucocorticoid effects. Since there are no definitive clinical studies directly addressing the relationship between the HPA axis and cardiovascular disease, we present indirect evidence from two types of studies: (1) studies that examine the cardiovascular effects of exogenous glucocorticoids, and (2) studies demonstrating that endogenous glucocorticoid activity varies between individuals. The effects of physiologic increases in endogenous glucocorticoid activity may not always mirror the effects of supraphysiologic glucocorticoids. Nevertheless, the known effects of exogenous glucocorticoids provide important insights into the putative effects of endogenous glucocorticoids.

Plasma B-type natriuretic peptide levels in ambulatory patients with established chronic symptomatic systolic heart failure.

BACKGROUND: The diagnostic and prognostic values of plasma B-type natriuretic peptide (BNP) testing are established. However, the range of plasma BNP levels present in the setting of chronic, stable systolic heart failure (HF) is unclear. METHODS AND RESULTS: We followed up 558 consecutive ambulatory patients with chronic, stable systolic HF (left ventricular ejection fraction <50%) treated at a specialized outpatient HF clinic between November 2001 and February 2003. Retrospective chart review was performed to determine clinical and functional data at the time of BNP testing (Biosite Triage). The clinical characteristics of patients with plasma BNP levels <100 pg/mL and those with > or =100 pg/mL were compared. In our cohort, 60 patients were considered asymptomatic, and their plasma BNP levels ranged from 5 to 572 pg/mL (median, 147 pg/mL). Of the remaining 498 symptomatic (NYHA functional class II-III) patients, 106 (21.3%) had plasma BNP levels in the "normal" diagnostic range (<100 pg/mL). Patients in this "normal BNP" subgroup were more likely to be younger, to be female, to have nonischemic pathogenesis, and to have better-preserved cardiac and renal function and less likely to have atrial fibrillation. CONCLUSIONS: In the ambulatory care setting, both symptomatic and asymptomatic patients with chronic, stable systolic HF may present with a wide range of plasma BNP levels. In a subset of symptomatic patients (up to 21% in our cohort), plasma BNP levels are below what would be considered "diagnostic" (<100 pg/mL).

Moricizine induced increase in pacing threshold.

A 72-year-old woman who was experiencing incessant ventricular tachycardia and recurrent automatic implantable cardioverter defibrillator (AICD) firing despite amiodarone therapy was referred to the Cleveland Clinic Foundation. Myocardial ischemia and infarction were ruled out by standard means. Several antiarrhythmic medications were tried previously without success. Moricizine, 200 mg three times daily, was initiated and controlled the ventricular tachycardia. However, after the dose of moricizine was titrated upward, the patient became symptomatically bradycardic and the ECG exhibited 2:1 block of her paced rhythm and an increased ventricular pacing threshold.

The metabolic syndrome as a vicious cycle: does obesity beget obesity?

Most attempts at weight loss are frustrated by the body's propensity to maintain fat mass. There are genetic and environmental mechanisms behind this phenomenon, such as thrifty genes, sedentary lifestyle and abundant food resources. We will outline a physiologic mechanism that may perpetuate obesity once it develops. Specifically, we suggest that obesity-induced hyperinsulinemia facilitates fuel storage as fat. This can be exacerbated by high glucocorticoid activity, low growth hormone (GH) activity and the paradoxical increase in free fatty acid (FFA) flux resulting from basal lipolysis in an expanded fat mass. We also outline mechanisms by which obesity may perpetuate low GH and increased glucocorticoid activity in the metabolic syndrome.

The metabolic syndrome: a tug-of-war with no winner.

The metabolic syndrome may be viewed as a state of insulin-counterregulatory overdrive: counterregulatory hormones and fatty acids chronically duel with insulin, causing a cascade of biochemical interactions resulting in insulin resistance, hypertension, and dyslipidemia. Even before beta cells fail and type 2 diabetes ensues, the deadly quartet is quietly rehearsing.