Assessment of coronary blood flow in humans using phase difference MR imaging

Coronary blood flow quantification provides essential information on the hemodynamic significance of coronary artery stenoses. Recently, magnetic resonance (MR) flow mapping has emerged as a new promising method to noninvasively determine flow velocity and flow volume within the coronary arteries. The aim of this study was to compare phase difference (PD) MR flow quantification with intracoronary Doppler flow measurements in 15 patients with suspected or known coronary artery disease. Flow quantification was attempted before and after systemic application of 5mg Isosorbiddinitrate (ISDN) in order to determine possible alterations in coronary flow volume. PD MR flow mapping was performed successfully in 13 of the 15 patients. For flow velocities and flow volume values, a close correlation between PD MR and Doppler flow measurements was found (r = 0.79 and r = 0.90, respectively). However, average flow measured by PD MR was significantly lower than the invasively obtained values (9.0 ± 4.4 cm/sec vs. 11.7 ± 4.9 cm/sec; p<0.001 and 46.3 ± 28.7 ml/min vs. 53.4 ± 32.8 ml/min; p<0.05). Although the mean flow volume remained constant in the entire patient group after ISDN application, individual changes (increase in 6, decrease in 4 cases) could be documented with PD MR imaging and showed a good correlation to the Doppler method (r = 0.82). In conclusion, PD MR flow mapping is a promising method for the noninvasive quantification of coronary blood flow and therefore offers the potential of assessing coronary artery stenoses. However, technical improvements are mandatory in order to increase accuracy of the method.     

Value and limitations of computer analysis of digital subtraction angiography in the assessment of coronary flow reserve

Conventional coronary angiography has significant limitations in quantifying the severity and functional significance of coronary stenoses. However, coronary reactive hyperemia is an excellent physiologic indicator of coronary reserve. Digital subtraction angiography offers the potential to analyze coronary blood flow dynamics quantitatively. Therefore we assessed the accuracy of digital angiographic methods to detect and quantify reductions in coronary flow reserve secondary to stenoses of varying magnitude in an experimental canine preparation. Studies were performed in nine anesthetized open-chest dogs with an electromagnetic flow (EMF) probe and two pneumatic occluders positioned on the left circumflex coronary artery. One occluder served to induce reactive hyperemia by temporary total occlusion, while the other served to produce variable gradations of stenosis. Digital angiography was performed after the subselective injection of contrast under basal conditions and during reactive hyperemia. Time-intensity curves were obtained from digital angiograms for both a coronary and a myocardial region of interest. Measurements included area under the curve, time to peak contrast, and contrast disappearance rate. An index of coronary reserve was computed as the ratio of hyperemic to basal measurements for each of these methods. Coronary blood flow ranged from 6.5 to 142 ml/min, with hyperemic to basal EMF flow ratios of 0.80 to 4.2:1. The index derived from contrast decay rate showed a poor correlation with EMF (r = .34). The correlation between measurements of time to peak myocardial contrast and coronary blood flow was r = .68 (y = 0.16 x + 0.97). The area under the time-intensity curve from a coronary region of interest showed a close correlation with coronary blood flow (y = 0.91 x + 0.1, r = .86). Thus estimates of coronary reserve by computer analysis of digital subtraction angiograms can yield information regarding the physiologic consequences of coronary stenoses.     

Do changes in blood flow in the subclavian artery affect flow volume in IMA grafts after complete arterial revascularization with the T-graft technique?

BACKGROUND: The T-graft procedure achieves complete arterial coronary revascularization with only two conduits. In this technique, all the bypass anastomoses are supplied by the left internal mammary artery (IMA). Changes in flow conditions or flow redistribution in the subclavian artery may thus sigificantly influence coronary perfusion. The objective of this study was to determine whether changes in blood flow in the subclavian artery affect the flow in IMA grafts in patients who have undergone complete arterial revascularization with T-grafts. METHODS: Quantitative flow volume and flow profiles in the IMA graft and the proximal subclavian artery were measured with a flow-wire in 20 patients one week postoperatively. Following baseline measurements, brachial artery constriction was achieved by applying a blood pressure measurement cuff to the patient's left upper arm. After 5 minutes, quantitative flow in the IMA and in the proximal subclavian artery was assessed. The cuff was then released and the measurements repeated. RESULTS: Flow in the subclavian artery changed significantly (p < 0.01) from baseline (355.4 +/- 95.2 ml/ min) to constriction (171.2 +/- 61.3 ml/min) and hyperemia (679.3 +/- 195.1 ml/min). Flow in the IMA graft remained constant irrespective of subclavian artery flow (75.4 +/- 26.2 ml/min vs. 78.0 +/- 28.9 ml/min vs. 75.5 +/- 29.3 ml/min, respectively). The flow profile in the IMA was similarily unchanged. CONCLUSION: In patients in whom the coronary bypass blood flow is dependent on the left IMA, neither the quantitative flow volume nor the flow profile are altered by changes in blood flow of the subclavian artery.     

Leptin causes nitric-oxide independent coronary artery vasodilation in humans.

Recent studies have shown that leptin causes vasodilation. However, it is unclear whether leptin causes coronary vasodilation in humans. To determine how leptin affects human coronary arteries and whether endothelium-derived nitric oxide (EDNO) is involved in the coronary arterial response to leptin, we infused leptin (0.3, 3 and 30 ng/kg/min) for 2 min into the left coronary ostium before and after an infusion of nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), in 11 men with angiographically normal coronary arteries. The diameter of the epicardial coronary arteries was quantitatively measured, and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. The changes in these parameters in response to leptin are expressed as the % change from the baseline values. Leptin caused coronary dilation (0.3 ng/kg/min: 2.0+/-0.5%; 3 ng/kg/min: 4.9+/-0.7%; 30 ng/kg/min: 3.8+/-0.9%) and increased CBF (13.6+/-3.3%, 36.8+/-5.6%, and 39.2+/-7.4%, respectively). After the infusion of L-NMMA, leptin also caused coronary dilation (2.0+/-0.4%, 4.5+/-0.7%, and 4.6+/-0.8%, respectively) and increased CBF (14.6+/-2.8%, 39.2+/-5.7%, 40.3+/-6.2%, respectively). Leptin-induced coronary vasodilation was not affected by the infusion of L-NMMA. These results suggest that leptin dilates coronary arteries in humans. Furthermore, EDNO may not contribute to leptin-induced coronary dilation.     

Transmural gradients of coronary flow reserve with physiologically and morphometrically defined stenoses in dogs

Coronary angiography permits identification of stenotic lesions but underestimates their severity and does not provide information regarding their physiologic significance. Evaluation of coronary flow reserve by means of selective coronary artery Doppler flow catheters or quantitative arteriography has been proposed to obtain this information. However, these techniques may not accurately reflect transmural gradients in flow. We evaluated the relationship between flow reserve defined with an epicardial Doppler flow probe and the transmural gradient of flow measured with radiolabeled microspheres in 21 dogs with graded stenoses and correlated results with coronary artery geometry measured morphometrically. Four groups of dogs were studied. In five control dogs without stenosis, reactive hyperemia after 20 seconds of complete coronary occlusion was 4.5 +/- 1.5 (mean +/- SD) times resting flow with an endocardial/epicardial flow ratio at peak flow of 1.0 +/- 0.2. When reactive hyperemia was blunted (without affecting resting flow) by 50% (n = 6), 75% (n = 5), or was abolished completely (n = 5) by coronary stenosis, the endocardial/epicardial flow ratio at peak flow was 1.0 +/- 0.3, 0.7 +/- 0.2, and 0.5 +/- 0.1, respectively. Cross-sectional area of the stenosed segment was reduced by 85.6 +/- 3.5%, 91.1 +/- 2.2%, and 92.8 +/- 4.3% in these groups, respectively. Thus in dogs with stenoses exceeding 86% of the cross-sectional area, endocardial flow reserve is compromised disproportionately compared with epicardial flow reserve, suggesting that clinical measurements of coronary flow reserve may underestimate the physiologic significance of coronary stenoses.     

Epicardial coronary artery constriction with intravenous ethanol

Although in vitro studies have demonstrated ethanol-induced coronary artery constriction, in vivo reports suggest an ethanol-related coronary dilator effect with increases in coronary blood flow. The principal difference in these studies is the demonstration of epicardial coronary constriction with ethanol, while dilation is described only in resistance vessels. Clinical studies have noted evidence of myocardial ischemia following ethanol ingestion in patients with coronary artery disease, suggesting ethanol-related constriction of diseased epicardial coronary arteries. This study hypothesized that intravenous ethanol would constrict canine epicardial coronary arteries while producing arteriolar resistance vessel dilatation. Ten closed-chest mongrel dogs weighing 24 +/- 1 kg (mean +/- SEM) were given 8 g of ethanol intravenously over 30 min. Left anterior descending and circumflex proximal artery diameters were measured by quantitative coronary angiography; myocardial flow was measured by Xenon washout, and myocardial flow distribution was measured with radioactive microspheres. Baseline proximal left anterior descending and circumflex artery areas were 6.3 +/- 0.5 and 5.8 +/- 0.4 mm2, respectively. Up to 30% left anterior descending and circumflex proximal artery narrowing was noted at 60 and 90 min following ethanol infusion. The constriction was reversed with nitroglycerin. There was a decrease in left anterior descending artery flow but no change in circumflex artery flow at 60 min. Blood ethanol level varied from 520 micrograms/ml initially to 205 micrograms/ml 90 min after the infusion terminated (intoxication = 1500 micrograms/ml). These data suggest that ethanol has significant vasoconstrictor action in vivo on epicardial coronary arteries.     

Alterations of phasic coronary artery flow velocity in humans during percutaneous coronary angioplasty.

BACKGROUND AND OBJECTIVES. Studies using Doppler catheters to assess blood flow velocity and vasodilator reserve in proximal coronary arteries have failed to demonstrate significant improvement immediately after coronary angioplasty. Measurement of blood flow velocity, flow reserve and phasic diastolic/systolic velocity ratio performed distal to a coronary stenosis may provide important information concerning the physiologic significance of coronary artery stenosis. This study was designed to measure these blood flow velocity variables both proximal and distal to a significant coronary artery stenosis in patients undergoing coronary angioplasty. METHODS. A low profile (0.018-in.) (0.046-cm) Doppler angioplasty guide wire capable of providing spectral flow velocity data was used to measure blood flow velocity, flow reserve and diastolic/systolic velocity ratio both proximal and distal to left anterior descending or left circumflex coronary artery stenosis. These measurements were made in 38 patients undergoing coronary angioplasty and in 12 patients without significant coronary artery disease. RESULTS. Significant improvement in mean time average peak velocity was noted in distal coronary arteries after angioplasty (before 19 +/- 12 cm/s; after 35 +/- 16 cm/s; p less than 0.01). Increases in proximal average peak velocity after angioplasty were less remarkable (before 34 +/- 18 cm/s; after 41 +/- 14 cm/s; p = 0.04). Mean flow reserve remained unchanged after angioplasty both proximal (1.5 +/- 0.5 vs. 1.6 +/- 1; p greater than 0.10) and distal (1.6 +/- 1 vs. 1.5 +/- 0.8; p greater than 0.10) to a coronary stenosis. Before angioplasty, mean diastolic/systolic velocity ratio measured distal to a significant stenosis was decreased compared with that in normal vessels (1.3 +/- 0.5 vs. 1.8 +/- 0.5; p less than 0.01). After angioplasty, distal abnormal phasic velocity patterns generally returned to normal, with a significant increase in mean diastolic/systolic velocity ratio (1.3 +/- 0.5 vs. 1.9 +/- 0.6; p less than 0.01). Phasic velocity patterns and mean diastolic/systolic velocity ratio measured proximal to a coronary stenosis were not statistically different from values in normal vessels (1.8 +/- 0.8 vs. 1.8 +/- 0.5; p greater than 0.10) and did not change significantly after angioplasty (1.8 +/- 0.8 vs. 2.13 +/- 0.9; p greater than 0.10). CONCLUSIONS. Flow velocity measurements may be performed distal to a coronary stenosis with the Doppler guide wire. Phasic velocity measurements made proximal to a coronary stenosis differed from those in the distal coronary artery. Both proximal and distal flow reserve measurements made immediately after angioplasty were of limited utility. Changes in distal flow velocity patterns and diastolic/systolic velocity ratio appeared to be more relevant than the hyperemic response in assessing the immediate physiologic outcome of coronary angioplasty.     

Measurement of maximal coronary flow reserve: a technique for assessing the physiologic significance of coronary arterial lesions in humans

Recent studies suggest that angiographic measurements of coronary arterial stenosis are poorly correlated with direct measurements of the capacity of the artery to conduct hyperemic blood flow. Direct measurement of coronary blood flow and the flow reserve capacity of individual coronary vessels in conscious humans, however, has been hampered by methodologic limitations. We have developed and validated a coronary Doppler catheter capable of subselectively measuring coronary blood flow velocity at the time of cardiac catheterization. Studies in seven calves demonstrated that measurements of the change in coronary blood flow velocity assessed using the Doppler catheter were highly correlated with simultaneous measurements of the change in coronary sinus blood flow (r = 0.97, slope = 1.06) and changes in blood flow velocity assessed using an epicardial Doppler probe (r = 0.95, slope = 1.04). Additional studies demonstrated that the catheter did not produce physiologically significant obstruction to coronary blood flow. Subsequent studies in 215 humans undergoing catheterization have shown that acceptable signals of phasic coronary blood flow velocity could be recorded in 176 patients. Subsequent dose response kinetic studies demonstrated that intracoronary administration of papaverine can rapidly produce maximal coronary hyperemia, equivalent in magnitude to intravenous dipyridamole, but short enough in duration to permit multiple measurements of coronary flow reserve during a single catheterization. Measurements of coronary flow reserve in patients with obstructive coronary artery disease have permitted characterization of the physiologic significance of individual obstructive coronary lesions. The development of this coronary Doppler catheter system and technique for measurement of maximal coronary flow reserve should facilitate characterization of the physiologic impact of coronary arterial lesions on coronary blood flow and studies of the coronary circulation in conscious humans.     

Importance of Nitric Oxide in the Coronary Artery at Rest and During Pacing in Humans

Objectives. The purpose of this study was to investigate the role of endothelium-dependent vascular regulation in the human coronary circulation during rest and hyperemic states.Background. Evidence of the role of nitric oxide (NO) during metabolic demand is not consistent in animal and human coronary circulation.Methods. N^G-Monomethyl-l-arginine (l-NMMA), a specific inhibitor of NO synthesis, was infused into the left anterior descending coronary artery at rest and during rapid atrial pacing in 18 subjects—9 with normal coronary arteries (control) and 9 with atherosclerotic coronary arteries. The diameter of the epicardial coronary artery was measured by quantitative coronary angiography. Vasodilation of the coronary microcirculation was assessed using an intracoronary Doppler FloWire.Results. Infusion of 25 μmol/min of l-NMMA reduced the diameter of the proximal and distal epicardial coronary artery segments by 8 ± 2% (mean ± SE) and 11 ± 2%, respectively (p < 0.05) in the control subjects. The coronary blood flow (CBF) decreased by 33 ± 13% during l-NMMA infusion. l-NMMA caused similar changes in the diameter of the distal epicardial segment and the CBF in patients with coronary artery disease. The proximal vessel diameter did not change significantly during infusion of l-NMMA. During pacing, infusion of l-NMMA caused the same changes in vessel diameter as before pacing in both groups, but did not affect CBF.Conclusions. Our findings indicate that NO synthesis maintains basal vasomotor tone in both conduit and resistance vessels in the normal human coronary circulation. Although NO release was impaired in the large epicardial coronary arteries in patients with atherosclerosis, NO still regulated vascular tone in the small epicardial coronary arteries and arterioles. Our results suggest that vasodilation in arterioles during increased myocardial oxygen demand is mediated by metabolic or myogenic mechanisms, or both, rather than by endothelium-dependent production of NO.(J Am Coll Cardiol 1997;29:85–92)>     

Definition of flow parameters in proximal nonstenotic coronary arteries using transesophageal Doppler echocardiography

Transesophageal echocardiography (TEE) enables the visualization of proximal coronary arteries. We investigated the feasibility of coronary flow evaluation using TEE, as well as to define flow parameters found in normal proximal coronary arteries. The subgroups of patients with normal proximal segments of coronary arteries were selected from the cohort of 210 patients undergoing routine coronary angiography. The left main coronary artery (LMCA), proximal segment of left anterior descending coronary artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA) were analyzed separately in 147, 64, 53, and 70 patients, respectively. Proximal coronary arteries were evaluated in the transverse plane using a 5-MHz TEE probe, and the flow in normal arteries was registered using pulsed-wave Doppler. The registration of flow with pulsed-wave Doppler was feasible in 88% of studies for the LMCA, 85% for the LAD, 58% for the LCx, and 65% for the RCA. Normal flow was laminar with distinct phasic character (diastolic predominance). Mean +/- SD values of peak coronary flow velocity were (systole/diastole) for the LMCA, 36 +/- 11/71 +/- 19 cm/sec; the LAD, 31 +/- 9/67 +/- 19 cm/sec; the LCx, 36 +/- 13/75 +/- 24 cm/sec; and the RCA, 25 +/- 8/39 +/- 12 cm/sec. Peak diastolic coronary flow velocity was most significantly correlated with heart rate. Doppler evaluation of proximal coronary flow is feasible using TEE in the majority of patients. The knowledge of normal flow values, which is different for the left and the right coronary artery, provides the background for proper interpretation of flow in diseased coronary arteries.     

Effect of basal epicardial tone on endothelium-independent coronary flow reserve measurement

Increased basal epicardial tone may attenuate the coronary flow reserve (CFR) by causing vasodilatation of resistance vessels. We examined the effect of basal epicardial tone on the endothelium-independent CFR measurements in subjects with nonobstructive coronary disease. Patients underwent evaluation of endothelium-independent CFR using adenosine (18–36 μg) and endothelium-dependent CFR using acetylcholine (10⁻⁶M-10⁻⁴M), both administered intracoronary. CFR to adenosine, presented as the ratio of Doppler flow velocities post- and pre-adenosine, was measured at baseline and after intracoronary nitroglycerin (200 μg). Nitroglycerin increased the coronary artery diameter by 19.7 ± 2.5%, and decreased the coronary vascular resistance from 3.0 ± 0.2 mm Hg/ml/min to 1.8 ± 0.1 mm Hg/ml/min (p < 0.0001). The response to adenosine at baseline and after nitroglycerin was similar (CFR ratio of 2.52 ± 0.09 and 2.57 ± 0.10, respectively, p = NS). The effect of nitroglycerin on the response to adenosine did not correlate with coronary endothelial function (r² = 0.06, p = 0.13). The basal epicardial tone does not affect CFR measurements in patients with angina and nonobstructive coronary disease. Cathet. Cardiovasc. Diagn. 44:392–396, 1998. © 1998 Wiley-Liss, Inc.     

Endogenous and exogenous catecholamines can accentuate myocardial ischemia only when coronary blood flow is below a critical level

Seventy-eight dogs with graded constriction of the left main coronary artery were studied to determine the coronary blood flow at which the heart is vulnerable to catecholamine induced ischemia. The left main coronary artery was cannulated with a Griggs' type self-perfusing cannula. The coronary blood flow (CBF) was reduced by graded constriction of the extra-corporeal circuit connected with this cannula. Blood flow rates between 12 and 117 ml/min/100 g were studied. Cardiac activation was achieved by either intracoronary administration of a physiological dose of catecholamine (noradrenaline; 0.4 microgram/kg/min or adrenaline; 0.2 microgram/kg/min), or by electrical stimulation of the left stellate ganglion (4 Hz, 2 msec, 10 V for 5 min). When CBF was below 30 ml/min/100 g, accentuated myocardial ischemia was always indicated by lactate production, myocardial creatine phosphate depletion, ischemic ST segment changes, and elevated left ventricular end diastolic pressure (LVEDP) during these stimulations. When CBF was above 50 ml/min/100 g, catecholamine clearly accelerated the cardiac function and myocardial metabolism with no signs of ischemia. When CBF was between 30 and 50 ml/min/100 g signs of accentuated myocardial ischemia appeared during catecholamine activation in only 1/2 of the dogs. This study indicated that the critical level for CBF at which endogenous or exogenous catecholamine can produce ischemia is between 30 and 50 ml/min/100 g.     

Determination of coronary flow reserve by parametric imaging

Nine mongrel dogs were instrumented with electromagnetic flow probes (EMF) to measure coronary blood flow through the left anterior descending (LAD) and left circumflex (LCx) coronary arteries at rest and after maximal coronary vasodilation (1 mg/kg/min adenosine). Relative coronary blood flow was determined by parametric imaging in the left posterior oblique projection using digital subtraction angiography (DSA). Transmural myocardial perfusion of the LAD and LCx beds was determined with tracer-labeled microspheres. Coronary flow reserve (maximal coronary blood flow divided by resting blood flow) was calculated under control conditions and after constriction of the proximal LAD or LCx by a screw occluder. Heart rate decreased significantly from 140 beats/min at rest to 122 beats/min after adenosine (p less than 0.001) and from 134 (rest) to 120 beats/min (adenosine; p less than 0.05) after coronary constriction. Peak systolic pressure was kept constant with an aortic constrictor. Left ventricular end-diastolic pressure increased significantly from 18 mm Hg at rest to 23 mm Hg (p less than 0.05) after coronary constriction. At baseline, coronary flow reserve was 4.2 with DSA, 3.8 with EMF, and 3.7 with microspheres; after coronary constriction, it was 2.6 (DSA), 1.9 (EMF), and 1.5 (microspheres) (all p less than 0.001 versus baseline). Coronary blood flow showed a good correlation between EMF and microspheres (r = 0.87, p less than 0.001), with a standard error of estimate (SEE) of 0.78 ml/g/min. Coronary flow reserve also showed a good correlation between EMF and microspheres (r = 0.82, p less than 0.001), with an SEE of 0.93. There was a moderate correlation between EMF and DSA (r = 0.68, p less than 0.001), with an SEE of 1.35 (40% of mean coronary flow reserve). The correlation coefficient between microspheres and DSA was 0.54 (p less than 0.01), with an SEE of 1.46 (39% of mean coronary flow reserve). The mean difference (accuracy) and standard deviation of difference (precision) were 0.2 +/- 1.0 between EMF and microspheres, -0.1 +/- 1.4 between EMF and DSA, and -0.6 +/- 1.7 between microspheres and DSA. We conclude that determination of coronary flow reserve by parametric imaging is associated with large variations that are greater than variations also inherent in the two reference techniques. Parametric imaging allows relatively accurate assessment of coronary flow reserve (small mean difference), but precision is low (large standard deviation of mean differences).(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin

OBJECTIVES: We examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries. BACKGROUND: It is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion. METHODS: Coronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL. RESULTS: Plasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 microg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = -0.30, p < 0.0001) and resistant (r = -0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 microg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes. CONCLUSIONS: The plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis.     

Comparison of transesophageal doppler coronary flow reserve measurements with thallium-201 single-photon emission computed tomography imaging in assessment of left anterior descending artery stenoses

Background and hypothesis: Recent studies demonstrate the feasibility of coronary flow reserve measurements by transesophageal echocardiographic (TEE) Doppler recordings of coronary sinus or left anterior descending (LAD) coronary artery flow velocity for detecting stenoses of the LAD artery. This study compares coronary flow reserve measurements by Doppler TEE with thallium-201 (²⁰¹T1) single-photon emission computed tomography (SPECT) in patients with proximal single-vessel LAD stenosis. Methods: Nineteen patients with various degrees of LAD stenosis (mean area stenosis 71 ± 24%; range 24-96%) were studied. Area stenosis by quantitative coronary angiography was < 75% in 7 patients and > 75% in 12 patients. Transesophageal LAD and coronary sinus Doppler measurements were performed at baseline and after intravenous dipyridamole. Coronary flow reserve was calculated as the ratio of hyperemic to baseline average peak velocities. Predefined coronary flow reserve cut-off values of 1.8 for the coronary sinus method and of 2.0 for the LAD method were used for diagnosis of significant LAD stenosis. Results were compared with qualitative ²⁰¹T1 dipyridamole SPECT. Results: Overall predictive accuracy for diagnosis of > 75% LAD stenosis was 79% for ²⁰¹T1 SPECT, 77% for the transesophageal LAD and 79% for the transesophageal coronary sinus technique. Concordant results between ²⁰¹T1 SPECT and the LAD and coronary sinus Doppler methods were observed in 79% and 71% of patients, respectively. Conclusions: Thallium-201 SPECT and transesophageal Doppler assessment of coronary flow reserve have similar accuracy for diagnosing significant proximal LAD stenosis. Therefore, both transesophageal Doppler techniques might constitute another widely available, noninvasive method for assessment of left coronary artery disease, if disease location is proximal.     

Intraoperative contrast echocardiography using sonicated iopromide (Ultravist 370) for imaging the post-bypass myocardial region

In order to minimize the rate of inadequate myocardial revascularizations, an intraoperative evaluation of regional myocardial perfusion could have practical impact. Current bypass flow measurements have inherent limitations and can determine only epicardial blood flow. To analyze regional graft-dependent myocardial blood flow an echocardiographic short-axis view of the left ventricle was performed intraoperatively in 11 patients undergoing elective coronary artery bypass surgery. After injection of 2 ml of sonicated lopromid (Ultravist 370) into 14 vein grafts, contrast enhancement in the corresponding myocardial regions was clearly visible, no side-effects occurred. Contrast decay halftimes (T/2) were determined by computer-assisted videodensitometry and compared to electromagnetic flow (EMF) rates, which were measured immediately before. T/2 ranged from 2.1 to 6.9 (mean 4.1 +/- 1.5) s and did not correlate to the EMF-rates of 55 to 100 (mean 80 +/- 16) ml/min. Thus intraoperative myocardial echocardiography is a safe and feasible method which allows on-line visualization and off-line quantitation of regional myocardial perfusion intraoperatively.     

Percutaneous, catheter-based coil embolization of coronary fistula: determination of hemodynamic relevance

A 55-year-old male with angina-like chest pain and positive thallium-scintigraphy was admitted to our hospital. Cardiac catheterization was performed for suspected coronary artery disease. The coronary angiogram showed no significant epicardial stenosis, but a large coronary fistula, connecting the left anterior descending artery with the pulmonary artery. Swan-Ganz catheter measurements, intracoronary Doppler, and quantitative coronary angiography were used to determine cardiac output, coronary blood flow, and coronary-to-pulmonary artery shunt fraction. These measurements showed a hyperdynamic cardiac output of 17 L/min, a coronary blood flow of 140 mL/min in the left anterior descending coronary artery with an estimated shunt fraction of 58% into the pulmonary circulation. Percutaneous, catheter-based coil embolization was performed to occlude the fistula. After embolization of one coil, coronary angiography showed the fistula's stump only. Cardiac output (9 L/min) and coronary blood flow (48 mL/min) were almost normalized. The patient was discharged from the hospital the day after the procedure. After a 6-month follow-up, there were still no complaints, angina-like symptoms or signs of myocardial ischemia in stress tests.     

Effects of synthetic human atrial natriuretic peptide on the human coronary circulation in subjects with normal coronary arteries.

Atrial natriuretic peptide (ANP) is recognized as an "endogenous vasodilator". The purpose of this study was to determine the effects of a clinical therapeutic dose of synthetic alpha-human ANP on the coronary circulation in 15 subjects with normal coronary arteries and normal ventricular function. The epicardial coronary arterial diameter was measured by selective coronary arteriography. Coronary blood flow was estimated from the arterial cross-sectional area and the flow velocity determined using an subselective intracoronary Doppler catheter. ANP, 0.03 micrograms/min/kg given intravenously over 15 minutes, caused a dilation of the large epicardial coronary artery (n = 8): the diameter of the proximal left anterior descending artery dilated from 2.6 +/- 0.4 to 3.1 +/- 0.5 mm (p less than 0.01). Mean arterial pressure decreased from 89 +/- 5 to 83 +/- 5 mmHg (p less than 0.01); heart rate did not change during ANP infusion. Estimated coronary blood flow significantly increased (n = 6, p less than 0.01), and thus the coronary vascular resistance decreased after ANP infusion, suggesting an ANP-induced dilation of resistance vessels. The present study demonstrates that in human subjects a clinical dose of ANP by intravenous infusion dilates both the large epicardial and small resistance coronary vessels. These results suggest a potentially beneficial role for ANP in reducing the severity of myocardial ischemia in patients with ischemic heart disease.     

Evidence of pathological coronary flow patterns in patients with isolated coronary artery aneurysms

OBJECTIVES: Aim of our study was to evaluate the coronary flow patterns and therapeutic effects of nitroglycerin (NTG) in patients with isolated large coronary artery aneurysms (CA). CA are defined as nonobstructive lesions of the epicardial coronary arteries with a luminal dilation >or=two-fold of the normal diameters. The pathophysiology of a potential coronary insufficiency in this entity is still unknown. METHODS: A coronary sinus study with incremental atrial pacing before and after the administration of 0.2 mg NTG was performed in 19 patients with bilateral large fusiform nonstenotic CA to evaluate an exercise-induced myocardial ischemia. The average peak velocity in the aneurysmatic segment of the proximal left anterior descending artery was simultaneously measured by a 14/1000 inch Doppler flow wire. The coronary flow volumes and vascular resistances were calculated. RESULTS: Evidence of exercise-induced myocardial ischemia was found in all patients presenting with a frank cardiac lactate production (10.2+/-3.3%) which was significantly aggravated by NTG (26.0+/-7.5%, P<0.003). 0.2 mg NTG provoked a long-lasting and significant decrease in coronary flow volume (from 140.2+/-34.2 to 91.2+/-21.8 ml/min, P<0.002), a marked increase in coronary vascular resistance (from 0.62 to 0.92 mmHG x ml/min(-1), P<0.002) and an inadequate increase in coronary flow volume under cardiac pacing. CONCLUSION: CA were identified as an entity of nonobstructive ischemic coronary artery disease with an exercise-induced myocardial ischemia and impaired flow volume. NTG exerted an adverse vasoactive effect in CA.     

Validation in dogs of a rapid digital angiographic technique to measure relative coronary blood flow during routine cardiac catheterization

Assessment of the functional significance of anatomically defined coronary stenoses has been hampered by the lack of clinically applicable techniques of measuring coronary blood flow or flow ratios. A digital angiographic technique is reported that allows rapid analysis of relative regional coronary blood flow during routine cardiac catheterization. This technique was validated in dogs by comparing digital flow ratio estimates with electromagnetic-flow (EMF) ratio measurements. Fourteen open-chest dogs had EMF probes placed on the proximal left anterior descending artery before selective coronary angiography. Electrocardiographically gated images were acquired directly by a digital radiographic system during both baseline blood flow and either contrast or papaverine-induced hyperemia. Dual-parameter functional images were generated using color and intensity coding to represent contrast arrival time and contrast density, respectively. For analysis, myocardial areas of interest were created over the distal perfusion bed of the left anterior descending coronary artery. Mean contrast density/appearance time (CD/AT) values were computer calculated as the mean density divided by the mean arrival time for each. Coronary flow reserve was determined as the ratio of the CD/AT value for a hyperemic image divided by the CD/AT value for the corresponding baseline image. CD/AT ratios correlated well (r = 0.92) with actual EMF ratios (CD/AT Ratio = 0.90 EMF Ratio +0.12, n = 48 ratios). Reproducibility was +/- 13%. Interobserver (r = 0.99) and intraobserver (r = 0.98) variability was excellent. Thus, rapid, accurate and reproducible estimates of relative regional coronary blood flow are possible using digital radiography.