Stephen Devries

Reproducibility of the measurement of coronary calcium with ultrafast computed tomography

The differences observed in repeated coronary calcium measurements underscores the importance of considering reproducibility issues when evaluating the significance of serial calcium scores. Furthermore, reproducibility data have important implications for planning intervention trials in which ultrafast computed tomography is used to monitor the evolution of atherosclerotic disease.

Influence of Age and Gender on the Presence of Coronary Calcium Detected by Ultrafast Computed Tomography

OBJECTIVES This study sought to determine the relation between coronary calcification detected with ultrafast computed tomography and lumen narrowing defined with angiography and evaluated whether this relation is influenced by age and gender. BACKGROUND Ultrafast computed tomography has been shown to be a sensitive method for detection of coronary calcification associated with atherosclerotic disease, but the relation between the extent of coronary calcification and degree of lumen narrowing and the possible influence of gender or age, or both, on this relation have not been clarified. METHODS Seventy men and 70 women were studied with ultrafast computed tomography for analysis of coronary calcification and coronary angiography. Coronary atherosclerosis was considered present if any lumen irregularity was noted on angiography, and obstructive coronary artery disease was defined as a lumen diameter narrowing > or = 70%. RESULTS Coronary calcification had a sensitivity of 88% for identification of patients with atherosclerotic disease and 97% for those with obstructive disease, with corresponding specificities of 55% and 41%, respectively. The sensitivity of coronary calcium for detection of atherosclerotic disease in women < 60 years old was 50%, significantly less than the 97% sensitivity in women > 60 years old and the 87% sensitivity in men < 60 years old (p < 0.05 for each comparison). Logistic regression analysis revealed a 1.81-fold increase in the likelihood of detecting coronary calcification in the atherosclerotic lesions of men compared with those in women (95% confidence interval 1.12 to 2.93, p = 0.016) when controlled for age and severity of coronary disease by angiography. CONCLUSIONS Atherosclerotic lesions in women are less likely to have coronary calcium than lesions with a similar degree of lumen narrowing in men. Differences in the pattern of coronary calcification between men and women may provide insight into the gender differences observed in the clinical development of symptomatic coronary artery disease.

Early detection of myocardial reperfusion by assay of plasma MM-creatine kinase isoforms in dogs.

To determine whether myocardial reperfusion can be detected promptly by changes in profiles of isoforms of MM-creatine kinase (CK) in plasma, coronary occlusion was induced in 30 conscious dogs and reperfusion was initiated after 1, 2, 3, or 4 hr in 21. The myocardial isoform of MM-CK, MMA, was quantified in serial plasma samples by chromatofocusing. Before coronary occlusion, MMA comprised 13 +/- 7% (SD) of the total CK activity in plasma. The percentage of MMA (MMA%) was elevated before reperfusion, but increased markedly and consistently to a peak of 52 +/- 13% (n = 21) between 30 min and 1 hr after the time of onset of reperfusion. The rate of increase in MMA% was significantly faster with reperfusion at 1 hr (1.44 +/- 0.42% min-1), 2 hr (1.28 +/- 0.45% min-1), or 3 hr (1.02 +/- 0.27% min-1) (p less than .001), but not with reperfusion at 4 hr (0.48 +/- 0.34% min-1) compared with the rate in nonreperfused control dogs (0.29 +/- 0.09% min-1). Furthermore, the rate of increase in MMA% was neither influenced by peak total CK activity (r = -.1) nor dependent on infarct size measured histochemically 24 hr after coronary occlusion (r = -.003). The time from coronary occlusion to the peak of MMA% was reduced by reperfusion at 1 to 3 hr compared with control, but this index was not identified as rapidly as the rate of increase in MMA%. Accordingly, characterization of the rate of increase in MMA% in plasma when reperfusion occurs early after the onset of myocardial infarction permits prompt, reliable, and noninvasive detection of myocardial reperfusion.

Diets to Prevent Coronary Heart Disease 1957-2013: What Have We Learned?

Our understanding of the potential cardioprotective properties of nutrition is relatively recent, with most relevant studies completed in the last several decades. During that time, there has been an evolution in the focus of nutritional intervention. Early trials emphasized reduction of dietary fat with the goal of preventing heart disease by reducing serum cholesterol. Results from trials focused exclusively on dietary fat reduction were disappointing, prompting subsequent studies incorporating a whole diet approach with a nuanced recommendation for fat intake. The Mediterranean-style diet, with a focus on vegetables, fruit, fish, whole grains, and olive oil, has proven to reduce cardiovascular events to a degree greater than low-fat diets and equal to or greater than the benefit observed in statin trials.

A Deficiency of Nutrition Education in Medical Training

1 Gaples Institute for Integrative Cardiology, Deerfield, Illinois and Division of Cardiology, Northwestern University, Chicago, Illinois; 2 Weil Foundation, University of Arizona College of Medicine, Tucson, Arizona; 3 Samueli Institute, Alexandria, Virginia and Harvard School of Public Health, Department of Nutrition, Boston, Massachusetts; 4 Arizona Center for Integrative Medicine, College of Medicine, University of Arizona, Tucson, Arizona; 5 Preventive Medicine Research Institute, Sausalito, California and Department of Medicine, University of California, San Francisco, California; 6 Section of Integrative Medicine and Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico; 7 Department of Family Medicine, University of Texas Medical Branch, Galveston, Texas; 8 Arizona Center for Integrative Medicine, College of Medicine, University of Arizona, Tucson, Arizona; 9 Departments of Nutrition and Epidemiology, Harvard School of Public Health; Channing Division of Network Medicine, Brigham and Womens Hospital and Harvard Medical School

Trending Cardiovascular Nutrition Controversies.

The potential cardiovascular benefits of several trending foods and dietary patterns are still incompletely understood, and nutritional science continues to evolve. However, in the meantime, a number of controversial dietary patterns, foods, and nutrients have received significant media exposure and are mired by hype. This review addresses some of the more popular foods and dietary patterns that are promoted for cardiovascular health to provide clinicians with accurate information for patient discussions in the clinical setting.

Reduced forward output states affect the left ventricular opacification of intravenously administered Albunex

Albunex is an Food and Drug Administration-approved ultrasound contrast agent used for the enhancement of left ventricular endocardial borders. To determine the efficacy of intravenously administered Albunex with regard to left ventricular opacification (LVO), a retrospective analysis of 117 patients who received 202 injections of Albunex for enhancement of endocardial borders was done (dose 0.08 to 0.22 ml /kg). Patients were routinely referred to our echocardiography laboratory for stress echocardiography for standard indications. Optimized settings for contrast enhancement (3.5 MHz transducer frequency and maximum dynamic range) were used. Four observers graded LVO on a scale from 0 to 3 (0 = no Albunex seen in the ventricular cavity; 3 = Albunex densely seen in the ventricular cavity). Overall, LVO was reported in 166 (82%) of 202 injections or in 91 (78%) of 117 patients. A significant reduction in LVO was noted in patients with mitral regurgitation, tricuspid regurgitation, atrial fibrillation, systolic dysfunction, or pulmonary hypertension (increased pulmonary artery systemic pressure). LVO was seen in 88% of the patients without these conditions. However, only 12 (44%) of 27 patients with one or more of the above conditions had LVO (p < 0.05). LVO can be achieved in the majority of patients after intravenously administered Albunex when imaged with optimal transducer settings. A subset of patients with systolic dysfunction, mitral regurgitation, tricuspid regurgitation, atrial fibrillation, or increased pulmonary artery systemic pressure has less effective LVO with Albunex. Heart disease associated with decreased forward flow appears to be associated with diminished LVO.

Optimizing Albunex in the left ventricle: An analysis of the technical parameters of four ultrasound systems in canines and humans

Albunex, an intravascular ultrasound contrast agent, has been used clinically to enhance echocardiographic images. The purpose of this study if (1) to determine whether varying the settings on commercially available ultrasound machines has an effect on left ventricular opacification after intravenously administered Albunex and if there is an effect on left ventricular opacification and (2) to determine the ideal settings for each ultrasound scanner. Six canine hearts were imaged with 1 ml injections of intravenously administered Albunex while varying the transducer frequency, preprocessing curves, postprocessing curves, and dynamic range on a variety of ultrasound units. Subsequently 50 human subjects underwent imaging with the various machines while the dynamic range and transducer frequencies were altered. All subjects received two or three intravenous injections of 10 ml Albunex. The opacification of the left ventricular cavitary images in both parts of the study were interpreted visually on a scale of 0 to 4 (0 = none, 1 = trace, 2 = moderate, 3 = dense, and 4 = ideal) by four observers. The maximum compression and transducer frequency of 3.5 MHz showed significant improvement of left ventricular opacification in both canines and humans. These studies have shown that (1) varying the ultrasound units parameters affects the quality of left ventricular imaging when Albunex is used to enhance the image, and (2) higher compression and a transducer frequency of 3.5 MHz tend to enhance Albunex images of canine and human hearts.

Determinants of clearance of tissue-type plasminogen activator (t-PA) from the circulation

Abstract Elucidation of determinants of the clearance of tissue-type plasminogen activator (t-PA) from the circulation is necessary in order to identify subjects in whom dose regimens will require modification in order to maximise safety and efficiency. Preliminary observations in hepatectomised animals suggest that the liver is a primary site of metabolism of t-PA. To determine whether alterations in hepatic blood flow simulating those encountered clinically in patients with congestive heart failure affect the rate of clearance of t-PA from plasma, t-PA was administered intravenously to nine dogs before and after hepatic blood flow had been reduced by induction of systemic hypotension. Hepatic blood flow was evaluated sequentially by analysis of the plasma clearance of carbon-l4 labelled taurocholic acid, a novel tracer selected because of its high hepatic extraction fraction. The extraction fraction of t-PA by the liver was measured directly by assay of the concentration of t-PA in simultaneously obtained arterial and hepatic venous blood samples. Both the concentration of t-PA antigen and t-PA functional activity were determined. t-PA was cleared from plasma in a bi-exponential manner with an early brisk (α) and a relatively less steep brisk (β) phase. At baseline, the half-life ( t , 1 2 ) of t-PA during the α-phase was 3.5±0.2 (±SEM) min. It did not change appreciably, averaging 4.4±0.6 min, despite marked reduction of hepatic blood flow accompanying profound hypotension with a 45%) reduction of mean arterial pressure. Similarly, the half-life of t-PA during the β-phase of clearance at baseline (12.6±1.1 min) was not significantly altered by reduction of hepatic blood flow (12.5 ± 0.9 min). The hepatic extraction fraction of t-PA declined progressively with time after administration of bolus of t-PA from 41±27%-0 (n = 3) 1 min after injection to 34 ± 16%, (n = 4), 14 ± 13% (n = 6) and 10 ± 11% (n = 6) 12, 20 and 30 min after injection in normotensive animals. Overall, the extraction fraction of t-PA by the liver increased 66.2±19.2% above the baseline level when hypotension was present compared to the case with normotension. This increase in extraction fraction associated with a diminution of hepatic blood flow probably accounts for the relatively consistent rate of clearance of t-PA from the circulation despite reduction of hepatic blood flow. The results obtained indicate that the rate of clearance of t-PA from the circulation does not diminish markedly despite profound hemodynamic perturbations and reduction of hepatic blood flow to levels simulating those likely to be encountered in patients with severe cardiovascular disease. Accordingly, they suggest that major modifications in dosage will not be required to compensate for derangements in hepatic perfusion. The bi-exponential nature of clearance of t-PA from the circulation and the diminished hepatic extraction fraction as a function of time underscore the likelihood that accumulation of t-PA may be encountered with prolonged administration.

Enzymatic estimation of the extent of irreversible myocardial injury early after reperfusion

To determine whether the extent of infarction can be estimated enzymatically soon after reperfusion, the rate of increase of creatine kinase (CK) activity in plasma early after coronary recanalization was compared with infarct size in 18 dogs and 10 patients. In dogs, reperfusion was initiated 2 to 4 hours after coronary occlusion. CK activity was measured in serial plasma samples and infarct size was assessed histochemically at 24 hours. A substantial and consistent fraction of the total CK appearing in plasma over 24 hours (cumulative CK) appeared in plasma soon after reperfusion, i.e., 21 +/- 2% (SE) within 30 minutes and 38 +/- 3% within 1 hour. The rate of increase of plasma CK activity correlated closely with infarct size when CK release was measured during the first 30 minutes (r = 0.92) or 60 minutes (r = 0.92) after reperfusion (n = 18). Similarly, in patients the rate of increase of CK activity measured within 2.5 hours of the time of reperfusion was closely related to infarct size delineated by positron emission tomography 1 to 2 weeks later (r = 0.93). Thus the rate of appearance of CK in plasma early after reperfusion reflects the extent of irreversible injury ultimately sustained and provides a criterion likely to be useful for prospective identification of patients at high risk after coronary recanalization.