Robert A. Vogel

Guidelines for the Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery A Report of the International Brachial Artery Reactivity Task Force

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.

American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines

A 29-year-old Dominican man with a history of intravenous heroin use and hepatitis C presented with a 5-day history of fever, dyspnoea, haemoptysis, pleuritic chest pain, abdominal pain, haematochezia and haematemesis. Initial physical examination was significant for scleral icterus, generalised abdominal tenderness to palpation, melaena and blood-tinged sputum. Blood cultures grew Fusobacterium species. CT scan of the chest revealed multiple bilateral cavitary features in lung fields. At the same time, a neck ultrasound performed demonstrated thrombophlebitis in the right internal jugular vein, confirming the diagnosis of ‘Lemierre’s syndrome’. Treatment was with antibiotics and supportive care for 6 weeks.

Effect of a Single High-Fat Meal on Endothelial Function in Healthy Subjects

Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.

Automated quantitative coronary arteriography: morphologic and physiologic validation in vivo of a rapid digital angiographic method.

Quantitative coronary arteriography has been shown to be useful in assessing the extent of coronary disease, its functional significance, and its response to therapeutic interventions. Most current methods rely either on hand-drawn arterial contours or automatic edge-detection algorithms applied to 35 mm cineangiograms. To assess the performance in vivo of a new, fully automatic, rapid coronary quantitation program, dogs were instrumented with precision-drilled, plastic cylinders to create intraluminal stenoses in the left anterior descending and/or circumflex arteries, as well as with high-fidelity micromanometers and electromagnetic flow probes. Stenosis diameters ranged from 0.83 to 1.83 mm. Biplane, on-line, digital coronary angiograms and cineangiograms were recorded during standard selective coronary arteriography in the closed-chest preparation. The on-line digital images were analyzed in nonsubtracted and subtracted modes. Cineangiograms were digitized to allow coronary quantitation by the same computer program. There was an excellent correlation between known and measured minimal diameter stenoses (r = .87 to .98, SEE = 0.09 to 0.24 mm). Interobserver and intraobserver variability analysis showed high reproducibility (r = .90 to .97, SEE = 0.12 to 0.23 mm). The best results in both analyses were achieved by nonsubtracted digital imaging and the worst by cineradiography. Measures of percent diameter stenosis, percent area stenosis (geometric and videometric), and absolute minimal cross-sectional area (geometric and videometric) were all significantly correlated with independent measures of actual coronary flow reserve. This study provides direct anatomic and physiologic validation in vivo of a new and rapid coronary quantitation method suitable for analysis of both digital angiograms and cineangiograms.

American College of Cardiology/ European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines

This document has been developed as a Clinical Expert Consensus Document (CECD), combining the resources of the American College of Cardiology Foundation (ACCF) and the European Society of Cardiology (ESC). It is intended to provide a perspective on the current state of management of patients with hypertrophic cardiomyopathy. Clinical Expert Consensus Documents are intended to inform practitioners, payers, and other interested parties of the opinion of the ACCF and the ESC concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community. Topics chosen for coverage by expert consensus documents are so designed because the evidence base, the experience with technology, and/or the clinical practice are not considered sufficiently well developed to be evaluated by the formal American College of Cardiology/American Heart Association (ACC/AHA) Practice Guidelines process. Often the topic is the subject of considerable ongoing investigation. Thus, the reader should view the CECD as the best attempt of the ACC and the ESC to inform and guide clinical practice in areas where rigorous evidence may not yet be available or the evidence to date is not widely accepted. When feasible, CECDs include indications or contraindications. Some topics covered by CECDs will be addressed subsequently by the ACC/AHA Practice Guidelines Committee. The Task Force on Clinical …

Potential adverse cardiovascular effects from excessive endurance exercise.

A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity.

The postprandial effect of components of the Mediterranean diet on endothelial function.

OBJECTIVES This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.

Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men

Current National Cholesterol Education Program guidelines consider desirable total and low-density lipoprotein cholesterol levels to be < 200 and < 160 mg/dl, respectively, for healthy individuals without multiple coronary risk factors. To determine the extent to which these levels affect vascular function, we assessed flow-mediated (endothelium-dependent) brachial artery vasoactivity noninvasively before, during, and after cholesterol lowering (simvastatin 10 mg/day) in 7 healthy middle-aged men with cholesterol levels meeting current recommendations. Flow-mediated brachial artery vasoactivity was measured using 7.5 MHz ultrasound and expressed as percent diameter change from baseline to hyperemic conditions (1 minute following 5 minutes of blood pressure cuff arterial occlusion). Flow-mediated vasoactivity rose from 5.0 +/- 3.6% at baseline to 10.5 +/- 5.6%, 13.3 +/- 4.3%, and 15.7 +/- 4.9% (all p < 0.05) as cholesterol fell from 200 +/- 12 to 161 +/- 18, 169 +/- 16, and 153 +/- 11 mg/dl after 2, 4, and 12 weeks, respectively, of cholesterol-lowering therapy. Vasoactivity and cholesterol returned to baseline levels 12 weeks after simvastatin discontinuation. Overall, vasoactivity was found to correlate inversely with cholesterol levels (r = -0.47, p = 0.004). These data suggest that flow-mediated brachial artery vasoactivity responds rapidly to changes in cholesterol levels and that endothelial function improves by lowering cholesterol levels below recommendations of current guidelines.

Cholesterol lowering and endothelial function.

The pathophysiology of the association between cholesterol and atherosclerosis has been thought to involve the deposition, modification, and cellular uptake of cholesterol. We now believe that the process begins with vascular injury and involves inflammation and vessel remodeling. The vascular endothelium actively regulates vascular tone, lipid breakdown, thrombogenesis, inflammation, and vessel growth, all of which are important factors in the development of atherosclerosis. Endothelial dysfunction promotes atherosclerosis through vasoconstriction, monocyte and platelet adhesion, thrombogenesis, and cytokine and growth factor stimulation and release. An important component of endothelial dysfunction is reduced availability of nitric oxide, which is caused by low-density lipoproteins, especially if they are oxidized. This reduced availability appears to occur through a combination of decreased production, abnormal signaling, and increased destruction by oxygen-free radicals. Concurrently, endothelium-mediated vasoconstrictors, adhesion molecules, cytokines, growth factors, and thrombogenic factors, such as endothelin, are increased by oxidized low-density lipoprotein. Several studies have shown improvements in endothelial function with cholesterol lowering, which may explain the early and substantial reductions in major cardiovascular events associated with cholesterol lowering.

Intermittent, ambulatory dobutamine infusions in patients with severe congestive heart failure.

Thirteen ambulatory patients with severe congestive heart failure were treated with weekly, outpatient 48-hour infusions of dobutamine. All 13 patients had at least a 25% increase in cardiac output during initial dobutamine titration, with a corresponding improvement in systemic vascular resistance. Improvement in functional class was achieved in only seven patients. Additionally, only three patients survived the 26-week study period. Although no change in ventricular ectopy was noted during the initial dobutamine infusions, six patients experienced sudden death; three other patients died of progressive heart failure and one died from pulmonary embolism. These data suggest that chronic intermittent ambulatory dobutamine infusions are only partly successful in improving symptoms and probably do not prolong survival in patients with severe congestive heart failure. Administration of this form of therapy on a clinical basis should be undertaken cautiously until safety and efficacy are demonstrated in prospective, controlled trials.