Comparison of myocardial contrast echocardiography derived myocardial perfusion reserve with invasive determination of coronary flow reserve.

AIMS: Invasive measurements of coronary flow reserve (CFR) by Doppler flow wire are an established method for determining coronary blood flow physiology. Myocardial contrast echocardiography (MCE) is a potential non-invasive method for quantifying myocardial blood flow (MBF). However, few studies have compared MCE-derived myocardial perfusion reserve (MPR) with Doppler flow wire-derived CFR, measured simultaneously in human subjects. This study aimed to correlate MCE-derived MPR with Doppler flow wire-derived CFR. METHODS AND RESULTS: Ten patients with at least two angiographically normal coronary arteries underwent simultaneous invasive Doppler flow wire measurements and MCE imaging at rest and at peak hyperaemia. Hyperaemia was induced by intravenous adenosine infusion. Doppler-derived CFR was calculated as the ratio of hyperaemic to baseline average peak red blood cell velocity. MPR was calculated as the hyperaemic to baseline ratio of the following parameters: myocardial blood volume (MBV), myocardial microbubble velocity (MMV), and MBF. MCE was performed using real-time and triggered imaging with contrast infused intravenously by bolus and continuous methods. Regardless of whether the contrast was infused by bolus or continuous methods, Doppler flow wire-derived CFR had a stronger correlation with MPR derived by MBV (r=0.8, P=0.05) than with MPR derived by microbubble velocity (r=0.3, P>0.05) or MBF (r=0.4, P>0.05). Real-time imaging with continuous infusion provided better correlation with CFR than triggered imaging methods or bolus administration. CONCLUSION: Myocardial perfusion reserve derived by real-time infusion MBV measurements correlates with Doppler flow wire-derived CFR. Therefore, MPR may be a potential surrogate for Doppler flow wire-derived CFR in patients with angiographically normal coronary arteries.

Emergence of the bipolar cultural complex in Walt Whitman.

My main hypothesis in this paper(1) is that America's seminal poet, Walt Whitman, was trapped--like so many of his contemporaries--in 'cultural complexes' (Singer & Kimbles 2004) that he internalized, but that he found a way to transcend the splits inherent in these 'bipolar' (Perry 1970) organizations through his art. One way he accomplished this was through his aesthetic method of 'holding the opposites' between two poles of a slavery is wrong/white supremacy is justified cultural complex. In my paper, I provide evidence for some of the contradictions inherent in Whitman's character by examining the political splits of his times and explore how various Self symbols he produced through his poetry, particularly the figures he called 'Black Lucifer' and the Deus Quadriune--a quaternity symbol--facilitated his personal and cultural transformation. Finally, I demonstrate the relevance of my hypothesis to contemporary racism during the pre-Civil Rights period in the South through a clinical example, and I show how the Jungian method of 'holding the opposites' can be effectively practised in the transference/countertransference field of psychotherapy in general.

Serial changes in systolic and diastolic echocardiographic indices as predictors of outcome in patients with decreased left ventricular ejection fraction.

BACKGROUND: Echocardiographic estimation of left ventricular ejection fraction aids in predicting adverse outcomes in coronary artery disease. However, in patients with impaired left ventricular function, further risk stratification is difficult. METHODS: A 2 year retrospective review was performed to identify patients with ejection fraction < or=30%. Echocardiographic measures of systolic and diastolic function were independently performed offline. Outcome information, which included MI, stroke, or death, was obtained. The patient cohort identified those with follow-up having 1) a single echocardiogram and a subset 2) with an initial echocardiogram and a second echocardiogram at greater than one year follow-up. RESULTS: This study included 110 patients, ages 20-94. Mean follow-up time was 29+/-9 months. Ejection fraction did not predict cardiovascular events. LV mass predicted of mortality (p=0.03). Diastolic indexes of mitral inflow E wave was a significant predictor of outcome (p=0.05). Impaired diastolic filling grade 2, 3, or 4 showed a 76% event rate. Decreases in ejection fraction at follow-up were seen in those who had an event, with an average decrease in ejection fraction of 17% versus those who lived with no event of 1%. Changes in mitral inflow E wave and changes in E/A ratio were both significant predictors of outcome. CONCLUSIONS: These data indicate that echocardiographic measures of both systolic and diastolic function aid in risk stratifying patients with decreased ejection fraction. The changed detected in serial echocardiographic information may be important in treatment and secondary prevention of future events.

Efficacy of atropine as a chronotropic agent in heart transplant patients undergoing dobutamine stress echocardiography.

BACKGROUND: After heart transplant (HTX), the heart is completely denervated. While sympathetic reinnervation is likely to occur, there is conflicting evidence regarding parasympathetic reinnervation. Accordingly, it is unclear if atropine is efficacious as a chronotropic agent in HTX patients undergoing dobutamine stress echocardiography (DSE), since cholinergic cardiac stimulation is required for atropine to exert its effect. The purpose of this study was to demonstrate that atropine can sufficiently increase the heart rate (HR) in HTX patients undergoing DSE. METHODS: A retrospective review was performed on 68 HTX patients who underwent DSE as part of their routine annual HTX follow-ups. Dobutamine was administered in the standard fashion of 10, 20, 30, 40, 50 mcg/kg per minute with blood pressure and electrocardiographic monitoring. If target HR was not attained, atropine was administered to aid in achieving 85% of maximum age-predicted HR. RESULTS: Mean patient age was 58 +/- 10 years. Mean period since transplant was 9 +/- 4 years. Forty-seven (69%) patients received dobutamine only, and 21 (31%) required additional atropine to reach target HR. Of the 21 patients who received atropine, 10 (48%) reached target HR. Neither time from transplant, age, gender, resting HR, medications, nor atherosclerotic risk factors predicted responsiveness to atropine. Those responding to dobutamine had a significantly greater resting HR than those receiving additional atropine. CONCLUSIONS: The adjunctive use of atropine in HTX patients during DSE aids in reaching 85% of maximum predicted HR in some patients. Furthermore, resting HR may predict the additional need of atropine during DSE.

Improved visualization of aortic intima-media thickening with the use of perflutren lipid microspheres.

BACKGROUND: Transesophageal echocardiography (TEE) has been used to diagnose atherosclerotic disease for patients who present with systemic embolic events. The primary aim of this study was to assess the supplemental value of echocardiographic contrast to standard TEE in identifying the aortic intima-medial thickness. METHODS: An aorta phantom was used to validate the accuracy of border delineation with and without contrast during TEE imaging. In all, 44 patients underwent TEE imaging of the thoracic aorta with a subsequent administration of a 0.3-mL bolus of perflutren lipid microspheres (Definity). Precontrast and postcontrast images were analyzed semiquantitatively for border delineation and quantitatively for intima-medial thickness and cross-sectional area. RESULTS: Wall thickness in the aortic phantom model with contrast was smaller, more accurate, and more reproducible to the true measurement. The clinical studies reflected similar results with average contrast intima-medial thickness measured at 0.15 +/- 0.08 cm and noncontrast at 0.18 +/- 0.08 cm (P < .01). The lateral wall showed the greatest improvement with a score of 1.23 increasing to an average of 1.82 (P < .001) with contrast. The medial, anterior, and posterior walls improved to an average 1.98, 1.39, and 2.0, respectively (P = .01). CONCLUSIONS: Contrast agents provide better aortic intima-media enhancement during TEE.

The influence of obstructive sleep apnea on FFR measurements for coronary lesion assessment.

Fractional flow reserve (FFR) determinations have been demonstrated to be largely independent of changes in systemic hemodynamic changes. Herein, we describe a case of obstructive sleep apnea cyclically altering FFR measurements from normal to abnormal in a patient with an intermediately severe coronary narrowing following treatment for an acute coronary syndrome. To eliminate uncertainty, FFR measurements should be made if possible during suspended respiration.

Small molecules for small minds? The case for biologic pharmaceuticals.

Biologic pharmaceuticals are gaining in both market share and clinical utility compared with small molecule therapeutics. This market growth is, in part, reflective of a field of science entering its toddlerhood, where with increased maturity, both development timelines and costs of manufacturing for these complex molecules will decrease, further enhancing the profitability side of the equation. Although a firm understanding of the rules governing toxicity (especially antibody responses to therapeutic proteins) remains to be defined, it is clear that proteins are less prone to much of the idiosyncratic toxicity associated with small molecule drug candidates. Proteins are disadvantaged in that they are unlikely to find much use in targeting intercellular processes; however, they have clear strengths over small molecules in targeting protein-protein interactions and the specific targeting of surface features of particular cells (e.g., in oncology). As each aspect of protein pharmaceutical technology advances, it is clear that this will be the major area for growth in the industry over the next decade.

Lack of relation between imaging and physiology in ostial coronary artery narrowings.

This study compared ostial lesion angiographic severity with physiologic assessment and showed that, for diameter narrowings >70%, fractional flow reserves were >0.75 in 20 of 25 lesions and >0.75 in 30 of 30 lesions with <70% diameter narrowings. Using fractional flow reserve in all ostial narrowings > or =70% may prevent patients from undergoing unnecessary interventions.

Coronary hyperemic dose responses of intracoronary sodium nitroprusside.

BACKGROUND: Sodium nitroprusside is one of several agents considered effective for treating the no-reflow phenomenon during acute coronary interventions. However, the coronary hyperemic dose responses and systemic hemodynamic effects of intracoronary nitroprusside have yet to be determined in humans. The purpose of this study was to compare the hyperemic and hemodynamic responses of intracoronary nitroprusside to intracoronary adenosine in patients during cardiac catheterization with angiographically normal anterior descending arteries. METHODS AND RESULTS: In 21 patients, coronary blood flow velocity (0.014-inch Doppler flow wire), heart rate, and blood pressure were measured in unobstructed left anterior descending coronary arteries at rest, after intracoronary adenosine (30- to 50-microg boluses), and after 3 serial doses (0.3-, 0.6-, and 0.9-microg/kg boluses) of intracoronary nitroprusside. Coronary reserve was calculated as hyperemia/basal coronary flow velocity. In an additional 9 patients with intermediate stenoses (53+/-7%), 14 fractional flow reserve (FFR) measurements (using 0.014-inch pressure wire) were performed with both intracoronary adenosine and nitroprusside (0.6 microg/kg). Intracoronary nitroprusside produced equivalent coronary hyperemia with a longer duration ( approximately 25%) compared with intracoronary adenosine. Intracoronary nitroprusside (0.9 microg/kg) decreased systolic blood pressure by <20%, with minimal change in heart rate, whereas intracoronary adenosine had no effect on these parameters. FFR measurements with intracoronary nitroprusside were identical to those obtained with intracoronary adenosine (r=0.97). CONCLUSIONS: Compared with adenosine, intracoronary nitroprusside produces an equivalent but more prolonged coronary hyperemic response in normal coronary arteries. Intracoronary nitroprusside, in doses commonly used for the treatment of the no-reflow phenomenon, can produce sustained coronary hyperemia without detrimental systemic hemodynamics. On the basis of FFR measurements compared with adenosine, sodium nitroprusside also appears to be a suitable hyperemic stimulus for coronary physiological measurements.

Current concepts in coronary physiology for the interventionalist.

Coronary angiography remains the 'gold standard' for the diagnosis of epicardial coronary disease. However, precise quantification of stenosis severity is limited because of the complex three-dimensional geometry of epicardial plaques. To assist the angiographer in lesion assessment, several physiologic measurements have been developed to evaluate stenosis severity, including coronary flow reserve, relative coronary flow reserve and fractional flow reserve. Physiologic lesion assessment can also be an invaluable tool in coronary intervention, evaluating efficacy of angioplasty and stent deployment.