...the writing committees of the "ESC 2016 Guideline on the Diagnosis and Treatment of Acute and Chronic Heart Failure Developed With the Special Contribution of the HFA" (1) and the "2016 ...ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure" (2) concurrently developed recommendations for the incorporation of these therapies into clinical practice.
Atherosclerotic coronary arteries are prone to constriction but the underlying causes are incompletely understood. We tested the hypothesis that endothelin-1 (ET-1), a potent vasoconstrictor, ...contributes to the heightened tone of atherosclerotic human coronary arteries.
In 8 patients with coronary artery disease (CAD) and 8 patients with angiographically smooth coronary arteries (normal), we infused BQ-123, an antagonist of the ET(A) receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60 minutes. The infused artery in the CAD patients contained a >50% stenosis. Using quantitative angiography, we compared the dilation of the infused artery with another, noninfused coronary artery. To estimate the magnitude of the contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with that elicited by intracoronary nitroglycerin (200 microgram). BQ-123 induced significant dilation in the normal arteries (7.3% at 60 minutes, P<0.001 versus noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60 minutes, P<0.001 versus infused normal arteries). The dilation at stenoses was particularly pronounced (21.6% at 60 minutes, P<0.001 versus infused CAD arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39% of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of tone at stenoses (P<0.01).
ET-1 accounts for nearly all the resting tone in atherosclerotic coronary arteries, especially at stenoses. Inhibitors of ET-1, by relieving constriction, may significantly lessen the hemodynamic significance of coronary stenoses and thereby reduce myocardial ischemia.
Endothelial function is thought to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. In the 1990s, high-frequency ultrasonographic imaging of the brachial ...artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. The noninvasive nature of the technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. However, despite its widespread use, there are technical and interpretive limitations of this technique. State-of-the-art information is presented and insights are provided into the strengths and limitations of high-resolution ultrasonography of the brachial artery to evaluate vasomotor function, with guidelines for its research application in the study of endothelial physiology.
Objectives. We sought to determine whether the antioxidant vitamin C improves endothelium-dependent vasodilation of forearm resistance vessels in patients with insulin-dependent diabetes mellitus.
...Background. Endothelium-dependent vasodilation is impaired in patients with diabetes mellitus. Oxidatively mediated degradation of endothelium-derived nitric oxide contributes to abnormal endothelium-dependent vasodilation in animal models of diabetes mellitus.
Methods. The study group included 10 patients with insulin-dependent diabetes mellitus and 10 age-matched control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3 to 10 μg/min). Endothelium-independent vasodilation was assessed by intraarterial infusion of nitroprusside (0.3 to 10 μg/min). Forearm blood flow dose–response curves were determined for each drug infusion before and during concomitant infusion of vitamin C (24 mg/min).
Results. In diabetic subjects, endothelium-dependent vasodilation was augmented by the concomitant infusion of vitamin C (p = 0.001). Endothelium-independent vasodilation was not affected by the concomitant infusion of vitamin C (p = NS). In control subjects, vitamin C infusion did not affect endothelium-dependent vasodilation (p = NS).
Conclusions. Vitamin C selectively restores the impaired endothelium-dependent vasodilation in the forearm resistance vessels of patients with insulin-dependent diabetes mellitus. These findings indicate that nitric oxide degradation by oxygen-derived free radicals contributes to abnormal vascular reactivity in humans with insulin-dependent diabetes mellitus.
Peripheral artery disease (PAD) affects more than 200 million adults worldwide. Patients with lower extremity PAD have a heightened risk for cardiovascular events because of the systemic nature of ...atherosclerosis, and benefit from treatment with risk factor-modifying therapies. Limb symptoms in PAD include intermittent claudication and diminished walking ability. Arterial obstruction from atherosclerotic lesions initiates limb ischemia; however, decreased perfusion incompletely determines the clinical expression of PAD and its response to therapy. Potential mechanistic drivers of claudication in addition to arterial obstruction include inflammation, vascular dysfunction, reduced microvascular flow, impaired angiogenesis, and altered skeletal muscle function. An improved understanding of the pathophysiology of limb symptoms has the potential to accelerate development of novel therapeutic strategies to increase functional capacity in patients with PAD.
We previously showed that cardiac nitric oxide (NO) inhibits the positive inotropic response to beta-adrenergic stimulation in humans with left ventricular (LV) dysfunction. Whether this effect is ...specific to heart failure per se or is a generalized feature of normal human myocardium is unknown. We therefore tested the hypothesis that inhibition of cardiac NO potentiates the positive inotropic response to beta-adrenergic stimulation in patients with symptomatic LV failure but not in subjects with normal LV function.
We studied 11 patients with LV failure due to idiopathic dilated cardiomyopathy and 7 control subjects with normal LV function. The beta-adrenergic agonist dobutamine was infused via a peripheral vein before and during concurrent intracoronary artery infusion of acetylcholine, which activates the agonist-coupled isoforms of NO synthase, and N(G)-monomethyl-L-arginine, which inhibits all isoforms of NO synthase. Changes in contractility were assessed by measuring the peak rate of rise of LV pressure (+dP/dt). Dobutamine increased +dP/dt by 40+/-6% and 73+/-14% in patients with heart failure and control subjects, respectively. Acetylcholine inhibited the +dP/dt response to dobutamine to a similar degree in patients with heart failure and control subjects (-39 +/- 8% and -31 +/- 4%, respectively; P=NS). Infusion of N(G)-monomethyl-L-arginine potentiated the +dP/dt response to dobutamine by 51+/-15% (P=.01 versus dobutamine) in patients with heart failure but had no effect in control subjects (-6 +/- 4%; P=NS versus dobutamine; P=.0002 versus heart failure patients).
Inhibition of cardiac NO augments the positive inotropic response to beta-adrenergic receptor stimulation in patients with heart failure due to idiopathic dilated cardiomyopathy but not in control subjects with normal LV function.
With accelerating healthcare costs and the desire to achieve the best value (health benefit for every dollar spent), there is growing recognition of the need for more explicit and transparent ...assessment of the value of health care. ...from a societal policy perspective, a critical healthcare goal should be to achieve the best possible health outcomes with finite healthcare resources. ...costs may vary widely by practice setting, locality, and nationality, and over time. ...individuals bear the burden of adverse health outcomes, yet costs typically are shared by society (e.g., by families, employers, government, premium payers, fellow employees, taxpayers). Class I recommendations determined to be of low value would not be recommended as performance measures. Because the value of a given care practice will change if the cost or benefit of the practice changes, timely review and updates of guidelines will be even more important when value determinations are included in the guidelines.\n This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document.
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