The 6-min walk test (6MW) as an efficacy endpoint in pulmonary arterial hypertension clinical trials: demonstration of a ceiling effect.

BACKGROUND: PAH trials traditionally use 6MW as the primary endpoint. Concerns regarding a "ceiling effect" masking efficacy have led to exclusion of patients with milder disease from most trials (BL 6MW>450 m). STRIDE I evaluated the selective endothelin A receptor antagonist, sitaxsentan (SITAX), in a 12-week randomized, double-blind, trial (178 patients) employing placebo (PBO), 100 mg or 300 mg SITAX orally once daily in PAH and included patients with NYHA class II, congenital heart disease and a BL 6MW>450 m, groups often excluded from previous trials. METHODS: We analyzed 6MW effects For All Pts (intention-to treat) and those meeting Traditional enrollment criteria, defined as patients with NYHA class III or IV and 6MW< or =450 m at BL with idiopathic PAH or PAH related to connective tissue disease. The 100 mg and 300 mg SITAX arms are pooled based on similar treatment effects on 6MW. CONCLUSION: Existence of a "ceiling effect" is supported by these data. The magnitude of the treatment effect and statistical power when using 6MW as the endpoint. Comparisons between PAH trials that do not adjust for the effects of differing enrollment criteria require caution.

BRCA1/2 testing: complex themes in result interpretation.

Since the cloning of BRCA1 and BRCA2, genetic testing for breast and ovarian cancer susceptibility has become more widespread. However, interpretation of test results is not always straightforward. To illustrate this point, five vignettes adapted from actual cases are presented. As these cases demonstrate, in many high-risk families, a deleterious mutation in BRCA1 or BRCA2 is not identified in an affected proband. There are several potential explanations for such a finding, namely that an undetected mutation in BRCA1 or BRCA2 may exist, or there could be a mutation in a rare or undiscovered gene. In addition, the possibility that women with breast cancer represent sporadic cases within hereditary cancer families must also be considered. Finally, the occurrence of BRCA1/2 variants of uncertain significance, often missense mutations, further complicates the risk assessment. In some of these instances, extending testing to relatives can be helpful to clarify results. When hereditary breast cancer cannot be ruled out, individuals may still be at increased risk for cancer and therefore need to obtain appropriate surveillance. The process of genetic counseling is critical both before and after testing to ensure that patients understand the potential medical and psychosocial implications of testing and are aware of available options and resources. A multidisciplinary approach to service delivery, which includes clinicians in genetics and oncology, can facilitate patients' decision making and provide continued access to information and support.

Across the Spectrum: Case Studies in Genetic Counseling for Breast and Ovarian Cancer.

We present three vignettes based on participants counseled as part of a clinical research program. These include a young unaffected woman at risk for a familial mutation, a newly diagnosed breast cancer patient, and a woman with recurrent ovarian cancer. Through the use of detailed vignettes, multifaceted issues that arise in cancer genetic counseling are highlighted.

Magnetic resonance-based assessment of global coronary flow and flow reserve and its relation to left ventricular functional parameters: a comparison with positron emission tomography.

BACKGROUND: Measurement of coronary sinus blood flow (CSF) by phase-contrast magnetic resonance (PC-MR) imaging at rest and during hyperemia may allow noninvasive assessment of global coronary hemodynamics. METHODS AND RESULTS: Sixteen healthy volunteers (age, 22 to 32 years) were examined with MR and PET in random order within 1 to 2 days. At rest and during hyperemia (dipyridamole 0.56 mg/kg), CSF was measured by a cine PC-MR technique (temporal resolution, 40 ms; spatial resolution, 1.25x0.8 mm(2)), and myocardial blood flow (MBF) was measured by [(13)N]NH(3) PET. PET and MR agreed closely for coronary flow reserve (CFR; mean difference, 2.2+/-14.7%; Bland-Altman method). CSF divided by either total left ventricular mass or an estimate of drained myocardium (LVM(drain)) correlated highly with PET flow data (r=0.93 and 0.95, respectively) and with measures of oxygen demand, ie, heart rate, afterload-corrected fiber shortening, and peak systolic stress determined by MR (overall correlation coefficients, 0.81 and 0.87, respectively, multivariate analysis). CSF/LVM(drain) did not differ significantly from PET-derived MBF (difference, 3.6+/-16.6%). In orthotopic heart transplant recipients (n=9), CFR was reduced and blood supply-demand relationships at rest were shifted toward higher flows (P<0.0001). CONCLUSIONS: This integrated MR approach allows comprehensive assessment of autoregulated and hyperemic coronary flow and is suitable for serial measurements in patients. In transplanted hearts, elevated resting flow is the major cause of reduced CFR.

Ventricular contraction abnormalities in dilated cardiomyopathy: effect of biventricular pacing to correct interventricular dyssynchrony.

OBJECTIVE: To measure ventricular contractile synchrony in patients with dilated cardiomyopathy (DCM) and to evaluate the effects of biventricular pacing on contractile synchrony and ejection fraction. BACKGROUND: Dilated cardiomyopathy is characterized by abnormal ventricular activation and contraction. Biventricular pacing may promote a more coordinated ventricular contraction pattern in these patients. We hypothesized that biventricular pacing would improve synchrony of right ventricular and left ventricular (RV/LV) contraction, resulting in improved ventricular ejection fraction. METHODS: Thirteen patients with DCM and intraventricular conduction delay underwent multiple gated equilibrium blood pool scintigraphy. Phase image analysis was applied to the scintigraphic data and mean phase angles computed for the RV and LV. Phase measures of interventricular (RV/LV) synchrony were computed in sinus rhythm and during atrial sensed biventricular pacing (BiV). RESULTS: The degree of interventricular dyssynchrony present in normal sinus rhythm correlated with LV ejection fraction (r = -0.69, p < 0.01). During BiV, interventricular contractile synchrony improved overall from 27.5 +/- 23.1 degrees to 14.1 +/- 13 degrees (p = 0.01). The degree of interventricular dyssynchrony present in sinus rhythm correlated with the magnitude of improvement in synchrony during BiV (r = 0.83, p < 0.001). Left ventricular ejection fraction increased in all thirteen patients during BiV, from 17.2 +/- 7.9% to 22.5 +/- 8.3% (p < 0.0001) and correlated significantly with improvement in RV/LV synchrony during BiV (r = 0.86, p < 0.001). CONCLUSIONS: Dilated cardiomyopathy with intraventricular conduction delay is associated with significant interventricular dyssynchrony. Improvements in interventricular synchrony during biventricular pacing correlate with acute improvements in LV ejection fraction.

Perceptions of physical fitness in patients with heart failure.

This study examined the relationship between perceived physical condition and measured physical fitness and activity levels in 40 patients with moderate heart failure (HF). Self rated physical condition, physical activity, self efficacy, and quality of life were evaluated by self administered questionnaires. Functional capacity was examined by cardiopulmonary exercise testing and 6 minute walk test. We found that physical activity levels were low. Participation in moderate intensity recreational activity and physical fitness were associated with self efficacy. Perceived physical condition was associated with emotional well being and levels of energy and fatigue. We conclude that self efficacy may reflect physical condition and physical activity levels in this sample of HF patients and may be a simple indicator of physical ability. Because of the association between perceived physical condition and emotional well being, caution must be taken when using self reports of physical condition. Further study is needed to explore these relationships.

Coronary vasodilator effects of BNP: mechanisms of action in coronary conductance and resistance arteries.

Brain natriuretic peptide (BNP), a hormone secreted predominantly in ventricular myocytes, may influence coronary vascular tone. We studied the coronary vasodilatory response to BNP under physiological conditions and after preconstriction with endothelin-1 (ET-1) in anesthetized pigs. Average peak-flow velocity (APV) was measured using intracoronary Doppler, and cross-sectional area (CSA) was measured using intravascular ultrasound. Coronary blood flow (CBF) was calculated. Intracoronary BNP induced dose-dependent increases in CSA, APV, and CBF similar in magnitude to those induced by nitroglycerin (NTG). The magnitude of BNP-induced vasodilation was accentuated after preconstriction with ET-1. Pretreatment with either the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester or the cyclooxygenase inhibitor indomethacin attenuated the coronary vasodilator effect of BNP in resistance arteries without influencing epicardial vasodilation. Pretreatment with the ATP-sensitive potassium-channel blocker glibenclamide enhanced epicardial vasodilation in response to BNP. We conclude that BNP exerts coronary vasodilator effects, predominantly in epicardial conductance vessels. An accentuated vasodilatory response to BNP occurs in ET-1-preconstricted arteries. BNP-induced vasodilation in coronary resistance arteries may be partially mediated via nitric oxide and/or prostaglandin release.

Evaluation of acute dual-chamber pacing with a range of atrioventricular delays on cardiac performance in refractory heart failure.

OBJECTIVES: This study evaluated how variations in atrioventricular (AV) delay affect hemodynamic function in patients with refractory heart failure being supported with intravenous inotropic and intravenous or oral inodilating agents. BACKGROUND: Although preliminary data have suggested that dual-chamber pacing with short AV delays may improve cardiac function in patients with heart failure, detailed Doppler and invasive hemodynamic assessment of patients with refractory New York Heart Association class IV heart failure has not been performed. METHODS: Nine patients with functional class IV clinical heart failure had Doppler assessment of transvalvular flow and right heart catheterization performed during pacing at AV delays of 200, 150, 100 and 50 to 75 ms. RESULTS: Systemic arterial, pulmonary artery, right atrial and pulmonary capillary wedge pressures, cardiac index, systemic and pulmonary vascular resistances, stroke volume index, left ventricular stroke work index (SWI) and arteriovenous oxygen content difference demonstrated no significant changes during dual-chamber pacing with AV delays of 200 to 50 to 75 ms. There were also no changes in the Doppler echocardiographic indexes of systolic or diastolic ventricular function. The study was designed with SWI as the outcome variable. Assuming a clinically significant change in the SWI of 5 g/min per m2, a type I error of 0.05 and the observed standard deviation from our study, the observed power of our study is 85% (type II error of 15%). CONCLUSIONS: Changes in AV delay between 200 and 50 ms during dual-chamber pacing do not significantly affect acute central hemodynamic data, including cardiac output and systolic or diastolic ventricular function in patients with severe refractory heart failure due to dilated cardiomyopathy.

Comparison of adenosine to dipyridamole in degree of coronary hyperemic response in heart transplant recipients.

Transplant coronary vasculopathy is associated with endothelial dysfunction. Microvascular function, assessed as coronary flow reserve, has been reported to be normal. We used intracoronary ultrasound technology to simultaneously assess conductance and resistance vessel function in response to standard dosages of the vasodilators adenosine and dipyridamole. Coronary hemodynamic changes were assessed in 11 heart transplant recipients, at a mean duration of 784 +/- 516 days after transplantation, using a 3.2Fr or 4.3Fr, 30-MHz ultrasound imaging catheter over a 0.014-inch Doppler guidewire. Measures of coronary average peak flow velocity (APV) and coronary cross-sectional area (CSA) were used to calculate volumetric flow during intravenous infusions of adenosine (140 micrograms/kg/min over 4 minutes) and dipyridamole (140 micrograms/kg/min over 4 minutes). Flow reserve was assessed as a ratio of maximal pharmacologically induced flow to steady baseline flow before infusion. Increase in APV (261.9% vs 194.6%, p = 0.005), lumenal CSA (+11.8% vs +4.2%, p = 0.01), peak volumetric blood flow (515.8 vs 317.2 ml/min, p = 0.007), and coronary flow reserve (2.93 +/- 0.74 vs 1.99 +/- 0.53, p < 0.001) were higher with adenosine than dipyridamole. Both agents caused similar decreases in systemic blood pressure and little change in heart rate. Adenosine appears to be a more potent coronary vasodilator than dipyridamole in denervated human transplant subjects. Adenosine has a vasodilator effect at the epicardial and microvascular levels, resulting in an overall increase in volumetric flow. Flow reserve in response to both endothelium-independent agents is decreased in comparison with previously established values, but the attenuation is greater with dipyridamole.

Abnormal pulmonary artery pressure profile after cardiac transplantation: an exercise Doppler echocardiographic study.

This study was designed to test the hypothesis that pulmonary artery pressure at rest and during exercise differs between patients with a transplanted heart and normal subjects and to determine the mechanisms responsible for the difference. Twenty-one patients who had undergone heart transplantation 1.5 to 27 months earlier without current evidence of acute cardiac rejection and 25 normal subjects were studied by exercise Doppler echocardiography. Systolic pulmonary artery pressure was higher at baseline in heart transplant patients than in normal subjects, at 31.6 +/- 9 mm Hg (mean +/- SD) versus 22.5 +/- 4, respectively (p = 0.0001). The increase in systolic pulmonary artery pressure with exercise was 1.4 times higher in heart transplant patients and correlated with pretransplantation pulmonary vascular resistances (r = 0.55; p = 0.01). In contrast, cardiac index at baseline or during exercise did not differ between the two groups. Diastolic parameters and ejection fraction at baseline or during exercise did not correlate with systolic pulmonary artery pressure. In conclusion, Doppler exercise echocardiography offers an alternative, safe method hemodynamic study of the transplanted heart. Although an abnormal increase in left ventricular filling pressure with exercise has been well documented, further studies are needed to investigate and characterize potential abnormalities in pulmonary vascular tone in the transplanted heart.

Transcoronary and pulmonary vascular dynamics of endothelin-1 in heart transplant recipients.

BACKGROUND: Endothelin-1, a potent endothelium-derived vasoconstrictor peptide, has recently been shown to be elevated in heart transplant recipients and may be a participant in posttransplantation vasculopathy. METHODS: We measured peripheral venous endothelin-1 concentrations in eight heart transplant recipients and eight age- and gender-matched healthy controls. Subsequently, in 21 transplant recipients, right atrial, aortic, and coronary sinus plasma was obtained and endothelin-1 levels were measured. Potential correlations to donor and recipient age, cyclosporine levels, hemodynamic parameters, donor heart ischemic time, time from transplantation, and serum creatinine were examined. In eight more patients, right atrial levels of endothelin-1 were measured before and after endomyocardial biopsy to examine the effect of this procedure on endothelin-1 concentrations. RESULTS: Peripheral endothelin-1 concentrations were significantly higher in heart transplant recipients (45.6 +/- 1.8 versus 25.8 +/- 2.3, p < 0.001). Multiple regression analysis showed a significant correlation between right atrial endothelin-1 and pulmonary artery systolic pressure (r = 0.48), as well as serum creatinine (r = 0.52). No relation to blood pressure, right atrial pressure, pulmonary vascular resistance, recipient age, cyclosporine levels, or donor heart ischemic time was observed. In 11 patients, a 38% +/- 7% fall in endothelin-1 levels across the pulmonary bed was observed, suggesting extraction across the lung in these subjects. Nine patients had net release of endothelin-1 (95% +/- 26% rise) across the coronary vascular bed, whereas 12 patients showed net extraction (24% +/- 4% fall). Endomyocardial biopsy had no influence on endothelin-1 levels (prebiopsy: 48.3 +/- 1.7; postbiopsy: 42.3 +/- 2.34; p = Not significant). CONCLUSION: These findings suggest that endothelin-1 levels in transplant recipients may be influenced by renal function and may contribute to pulmonary hypertension. The significance of transcardiac release of endothelin in some patients is unclear: further studies are needed to determine the pathophysiologic significance of endothelin-1 in heart transplant recipients.

Cyclosporine impairs release of endothelium-derived relaxing factors in epicardial and resistance coronary arteries.

BACKGROUND: Cyclosporin A is reported to impair endothelium-mediated vasorelaxation and induce endothelin release in some noncoronary vascular beds. We wished to determine whether acute cyclosporine administration induces endothelial dysfunction in coronary conductance or resistance arteries. METHODS AND RESULTS: We examined the effect of intracoronary acetylcholine, N omega-nitro-L-arginine methyl ester (L-NAME), L-arginine, nitroglycerin, and adenosine before and after acute cyclosporine administration (3 mg/kg IV over 30 minutes) in anesthetized dogs. Flow velocity was measured with a 0.014-in Doppler wire to assess resistance vessel responses, and epicardial coronary lumen area was simultaneously measured with a 4.3F, 30-MHz imaging catheter inserted over the Doppler wire. In 6 dogs, acetylcholine-induced increase in flow velocity was attenuated by cyclosporine in vehicle (137% to 55% at 10(-5) mol/L, P < .001), as was acetylcholine-induced epicardial vasodilation (14.1% to 6.7% at 10(-5) mol/L, P < .001). Vasodilation in response to intracoronary nitroglycerin (200 micrograms) and adenosine (6 mg) were unchanged by cyclosporine. Epicardial vasoconstriction with L-NAME (10(-4) mol/L) was reduced by cyclosporine (Pre, 7.4 +/- 0.9%; Post, 2.6 +/- 1.2%; P = .04), but L-arginine (10(-4) mol/L) had no effect after cyclosporine. In another 5 dogs, pure cyclosporine impaired acetylcholine-induced vasodilatation to the same degree as cyclosporine in vehicle (Cremophor); vehicle infusion did not impair endothelial function. In 5 more dogs, cyclosporine did not increase either arterial or coronary sinus concentrations of endothelin-1. CONCLUSIONS: The present study shows that cyclosporine acutely impairs release of endothelium-derived relaxing factor in canine conductance and resistance coronary arteries and provides evidence for decreased epicardial nitric oxide release after cyclosporine. The potential contribution of acute cyclosporine-induced coronary endothelial dysfunction to posttransplant vasculopathy needs further study.

Effect of orthotopic cardiac transplantation on peripheral vascular function in congestive heart failure: influence of cyclosporine therapy.

The objective of this study was to examine peripheral vascular function before and after cardiac transplantation and to assess the effect of immunosuppressive therapy on peripheral vascular reactivity. Peripheral vascular function abnormalities present in congestive heart failure may be reversed with cardiac transplantation, but immunosuppressive therapy may alter these changes in the peripheral vasculature. Venous occlusion plethysmography was used to study peripheral vascular function in nine patients with severe congestive heart failure who underwent cardiac transplantation. Forearm blood flow and forearm vascular resistance were measured in patients with congestive heart failure in response to cold stimulation, maximal hyperemia, and hand grip exercise (1) before transplantation; (2) 24 to 36 hours posttransplantation before the commencement of cyclosporine; (3) 6 to 8 days posttransplantation in the presence of therapeutic cyclosporine levels; and (4) 6 weeks posttransplantation. Venous capacitance was also measured. After cardiac transplantation, mean arterial pressure increased and remained elevated. Forearm blood flow initially increased after transplantation but subsequently decreased with cyclosporine. Cold-induced reflex sympathetic activation decreased immediately after transplantation but was significantly enhanced with cyclosporine. The maximal vasodilatory response following ischemic cuff occlusion and with 5 minutes of isometric hand grip exercise increased significantly after transplantation and remained improved at 6 weeks. Thus after cardiac transplantation, peripheral vasodilator function improves and is not altered by cyclosporine. However, with cyclosporine therapy resting forearm vascular resistance increases and reflex sympathetic vasoconstriction is enhanced, suggesting that cyclosporine may potentiate adrenergic-mediated peripheral vasoconstriction and thus may contribute to posttransplant hypertension.

Nonglycoside inotropes in congestive heart failure. Are they beneficial or harmful?

Nonglycosidic adrenergic and nonadrenergic inotropic drugs improve systemic hemodynamics and left ventricular function in patients with severe congestive heart failure. As these beneficial effects are observed with short-term therapy, the use of these agents should be restricted to the treatment of acute heart failure. Long-term therapy with adrenergic agents as well as the phosphodiesterase inhibitors appears to enhance mortality in patients with chronic systolic heart failure. Potential indications for long-term therapy with nonglycosidic inotropic drugs include vesnarinone and ibopamine for selected patients with refractory heart failure or as pharmacologic bridges to cardiac transplantation.

Importance of oxygen-haemoglobin binding to oxygen transport in congestive heart failure.

OBJECTIVE: To assess the importance of 2,3-diphosphoglycerate (2,3-DPG) and oxygen-haemoglobin binding to oxygen transport in patients with congestive heart failure. METHODS: In 30 patients with severe congestive heart failure, arterial, mixed venous, and coronary sinus venous blood concentrations of 2,3-DPG were measured and systemic output and coronary sinus blood flow were measured by a thermodilution technique. Oxygen-haemoglobin affinity was expressed as the oxygen tension in mm Hg at which blood is 50% saturated with oxygen (P50). RESULTS: Compared with normal values, 2,3-DPG was high in arterial blood (2.58 mumol/ml, p = 0.01; 20.8 mumol/g haemoglobin, p < 0.0001). Significant gradients between arterial, mixed venous, and coronary sinus blood 2,3-DPG concentrations were also found (mixed venous = 2.40 mumol/ml, p = 0.05 v arterial blood; coronary sinus venous blood = 2.23 mumol/ml, p < 0.04 v arterial blood). P50 was correspondingly high compared with the accepted normal value (mean 29.7 mm Hg, normal 26.6 mm Hg, p < 0.001). Systemic oxygen transport (351 ml O2/min/m2) varied directly with the forward cardiac index (r = 0.89, p < 0.0001). There was no relation between systemic oxygen transport and arterial oxygen content. Similarly, myocardial oxygen transport was found to vary directly with coronary sinus blood flow. Calculations of changes in cardiac index and coronary sinus blood flow at normal oxygen-haemoglobin binding indicate that a considerable increase in cardiac index and coronary blood flow would be required to maintain similar systemic and myocardial oxygen transport. CONCLUSIONS: In patients with severe heart failure increased 2,3-DPG and reduced oxygen-haemoglobin binding may be compensatory mechanisms that maintain adequate systemic and delivery of oxygen to myocardial tissue.

Noninvasive assessment of the pulmonary artery pressure response to exercise after uncomplicated heart transplantation.

The pulmonary artery pressure response to exercise has been used as an index of cardiac reserve and frequently mirrors diastolic conditions. To define this response after orthotopic heart transplantation, we exercised 27 subjects on supine bicycle ergonometers. Stroke volume and pulmonary artery pressure were monitored with contrast-enhanced Doppler imaging. Study patients had undergone orthotopic heart transplantation. Seventeen patients were screened, and eight were subsequently determined by endomyocardial biopsy to be histologically free of acute cardiac allograft rejection. A control population of nonconditioned normal volunteers was also evaluated (heart transplant patients: n = 8, age = 45.7 +/- 7.3 years, seven men; normals volunteers: n = 10, age = 49.4 +/- 12.8 years, nine men; P = NS). Total exercise time and peak heart rate were reduced in heart transplant patients: 7.6 +/- 2.5 minutes, 123 +/- 4 beats/min versus normal volunteers: 16.2 +/- 4.5 minutes, 134 +/- 4 beats/min (P < 0.05). Change in stroke volume from baseline to peak exercise was greater in heart transplant patients: 29.9 +/- 4.6 ml versus normal volunteers: 3.9 +/- 5.7 ml (P < 0.01). No difference was observed in the pulmonary artery pressure response to exercise. In patients with uncomplicated heart transplantation a reduction in exercise capacity is shown; however, the pulmonary artery pressure response to exercise is comparable to normal subjects. A blunted heart rate response is observed, which is partially compensated by increases in stroke volume. These findings suggest that cardiac diastolic function is preserved and that denervation of the heart accounts for impaired exercise tolerance.

Cyclosporine-induced hemolytic uremic syndrome in a heart transplant recipient.

We report a case of hemolytic uremic syndrome associated with the use of cyclosporine in a heart transplant recipient. The patient manifested many classic signs and symptoms of hemolytic uremic syndrome, and a diagnosis was confirmed by kidney biopsy. Treatment with plasma exchange was effective in halting the hemolysis, but renal function failed to improve. Rechallenge with cyclosporine caused recurrence of microangiopathic hemolysis. Because of concerns regarding allograft rejection, an experimental immunosuppressive agent, RS-61443, was used that was effective in controlling rejection and was not associated with recurrence of hemolytic uremic syndrome.

Transvenous coronary ultrasound imaging. A novel approach to visualization of the coronary arteries.

BACKGROUND: Catheter-based ultrasound is a new imaging modality to examine endovascular detail in the coronary circulation. This technique requires direct placement of the catheter in the arterial segment of interest. METHODS AND RESULTS: We examined the feasibility of a less invasive approach by imaging the coronary arterial circulation by using a 5F (30 MHz) imaging catheter placed in the cardiac venous system. Using simultaneous fluoroscopy, we studied anesthetized closed-chest dogs (n = 6) and human subjects undergoing right heart catheterization (n = 11). After cannulation of the coronary sinus, the circumflex coronary artery (Cx) was visualized from the great cardiac vein (GCV), and on advancing the catheter into the anterior interventricular vein (AIV), the left anterior descending artery (LAD) was identified. Where artery and vein were parallel to each other, circular cross-sectional images of the coronary artery were obtained, whereas oblique and transverse orientation of artery to vein produced ellipsoid images or long-axis images. In the dogs, ultrasound-determined cross-sectional area of the coronary arteries (4.81 +/- 0.18 mm2) correlated closely with angiography (4.77 +/- 0.21 mm2) (r = 0.91, p less than 0.001). In humans, the Cx was readily visualized from the GCV in all subjects but because of anatomic variability, the LAD was seen less consistently from the AIV (73%). There was significant correlation between ultrasound-determined cross-sectional areas of the coronary arteries (8.25 +/- 0.34 mm2) with those from angiography (8.59 +/- 0.3 mm2) (r = 0.82, p = 0.001) in humans. In all subjects, the ultrasound transducer could be safely advanced into the AIV to the cardiac apex. Limitations of the technique include ultrasonic penetration problems, caused in part by the large size of human coronary veins and variability in artery-vein relations. CONCLUSIONS: We conclude that transvenous imaging of coronary arteries with intravascular ultrasound is a less invasive, promising new approach to the study of structure and morphology in the coronary vasculature.