Coronary Blood Flow Reserve Research Articles

Role of capillaries in determining CBF reserve: new insights using myocardial contrast echocardiography.

To define the role of capillaries in the control of coronary blood flow (CBF) reserve, we developed a model of the coronary circulation and evaluated experimental data in its context. Our model comprised three compartments connected in series (arterial, capillary, and venous), each with its own resistance. The resistance in each vascular compartment was derived from the model based on hemodynamic data obtained in nine dogs during baseline and stenosis, both at rest and during hyperemia. The capillary hydrostatic pressure was assumed to be constant in all stages. Although in the absence of stenosis, the contribution of capillaries to total myocardial vascular resistance was only 25 +/- 5% at rest, it increased to 75 +/- 14% during hyperemia, despite the total myocardial vascular resistance decreasing by 51 +/- 13%. In the presence of a noncritical stenosis, total myocardial vascular resistance decreased by 22 +/- 10% at rest, with no change in capillary resistance. During hyperemia, total myocardial vascular resistance increased by 58 +/- 50% in the presence of the noncritical stenosis. In this situation, because arteriolar and venular resistances were already minimal, the increase in myocardial vascular resistance was due to increased capillary resistance, making it the predominant source (84 +/- 8%) of total myocardial vascular resistance. Myocardial video intensity (VI) on myocardial contrast echocardiography (MCE), which reflects capillary blood volume, decreased distal to the stenosis during hyperemia. In the presence of a flow-limiting stenosis at rest, myocardial VI also decreased, indicating that decrease in CBF was associated with an increase in capillary resistance. Our findings also provide an alternative explanation for the critical coronary closing pressure. Thus, contrary to previously held notions, capillaries play a vital role in the regulation of CBF.

Lack of correlation between left ventricular mass and diameter of left coronary artery main trunk in hypertensive patients

The study was designed to evaluate whether the increase in left ventricular (LV) mass in essential hypertensives (H) is associated with a proportional increase in diameter of the left coronary artery (LCA) trunk. Twenty-six hypertensives, 14 with left ventricular hypertrophy (LVH) (left ventricular mass index [LVMI] ≥>134 g/m 2 in men and ≥110 g/m 2 in women) and 12 without LVH, and 10 normotensive controls (C) underwent clinical laboratory and echocardiographic transthoracic examination. LV dimensions were measured according to the Penn convention and LV mass calculated by the formula of Devereux. The LCA main trunk was visualized by two-dimension short axis view at the level of the great vessels section, and the diameter measured as intima–intima distance at end-diastole. Hypertensives with and without LVH and C had similar age, sex, and body surface area distribution. LVMI was, by definition, significantly higher in H with LVH than in H without LVH and in C (144 ± 21, 113 ± 13, and 98 ± 10 g/m 2, P < .01), whereas the diameter of the LCA trunk was similar in all groups (0.48 ± 0.1, 0.48, and 0.46 cm, respectively). There was no significant correlation between LVMI and LCA diameter in H (r = 0.21, P = not significant). The diameter of LCA trunk was significantly correlated only with BSA (r = 0.5, P < .01), LV end-systolic and end-diastolic diameters (r = 0.5 and r = 0.4, P < .05). Our data suggest that in H the increase in LVM is not associated with a concomitant increase of epicardial coronary artery diameter, and this finding may account in part for the impairment of coronary blood flow reserve in LVH.

MR measurement of coronary blood flow

The functional significance of coronary arterial stenosis can be evaluated by measuring the pharmacological flow reserve. Magnetic resonance (MR) imaging has a unique potential for noninvasive measurement of coronary blood flow and flow reserve in the native coronary artery and bypass graft. Restenosis after coronary balloon angioplasty and stenting in the left anterior descending artery can be detected noninvasively with serial MR measurements of the coronary flow reserve. Further refinement of the MR pulse sequences to improve spatial and temporal resolutions may permit accurate quantification of blood flow volume and flow reserve in all major coronary arterial branches. MR assessments of blood flow volume and flow pattern allow noninvasive detection of significant stenosis in the coronary artery bypass graft as well. By integrating MR blood flow measurement in the coronary sinus and cine MR assessment of left ventricular myocardial mass, altered myocardial micro-circulation in patients with diffuse myocardial diseases, such as hypertrophic cardiomyopathy and cardiac transplant, has been documented. J. Magn. Reson. Imaging 1999;10:728-733.

State of the Art lecture. Risk mechanisms in hypertensive heart disease.

In this report, some of the underlying pathophysiological alterations associated with the independent risk from hypertensive heart disease and left ventricular hypertrophy are discussed. Emphasized are the classically described coronary hemodynamic alterations of decreased coronary blood flow and flow reserve with increased coronary vascular resistance and minimal coronary resistance; more recent concepts of endothelial dysfunction are emphasized. Additionally, increased collagen deposition within the ventricular walls and perivascularly participates importantly. These changes are exacerbated by the aging process and perhaps by increased dietary salt intake. Consequences of these functional and structural changes include further endothelial dysfunction, impairment of coronary hemodynamics, and ventricular contractile function (diastolic as well as systolic). The clinical consequences of these alterations are angina pectoris (with or without atherosclerosis), myocardial infarction, cardiac failure, lethal dysrhythmias, and sudden cardiac death. Thus, not all that is clinically recognized as "left ventricular hypertrophy" is true myocytic hypertrophy with structural remodeling; other important comorbid changes occur that directly affect risk, including ventricular fibrosis, impaired coronary hemodynamics, and endothelial dysfunction.

Pharmacological stress testing

Pharmacological stress in conjunction with radionuclide myocardial perfusion imaging has become a widely used noninvasive method of assessing patients with known or suspected coronary artery disease. In the United States, over one third of perfusion imaging studies are performed with pharmacological stress. Pharmacological stress agents fall into two categories: coronary vasodilating agents such as dipyridamole and adenosine, and cardiac positive inotropic agents such as dobutamine and arbutamine. For both, in the presence of coronary artery disease (CAD), perfusion image abnormalities result from heterogeneity of coronary blood flow reserve. Vasodilating agents work directly on the coronary vessels to increase blood flow, whereas inotropic agents work indirectly by increasing myocardial work load, which then leads to an increase in coronary blood flow. Both classes of agents have high accuracies for diagnosing coronary artery disease, and they have excellent safety records with acceptably low occurrences of side effects. For dipyridamole planar thallium imaging, pooled analysis yields a sensitivity of 85% and a specificity of 87% for diagnosis of coronary disease, but there is a large variation in reported values depending on various factors, such as the extent of postcatheterization referral bias, the type of imaging (planar versus single photon emission computed tomography [SPECT]), the types of patients being studied (single versus multivessel disease, men versus women), and the imaging agent used (thallium versus one of the technetium-based agents). Diagnostic accuracies for adenosine are similar to those of dipyridamole, with reported overall sensitivities ranging from 83% to 97%, and specificities ranging from 38% to 94%. For dobutamine, pooled analyses yield a sensitivity of 82% and a specificity of 75%. There is some concern that dobutamine may interfere with uptake of technetium-99m sestamibi, lowering the sensitivity for detection of disease, and thus the vasdodilating agents are generally preferred. Pharmacological stress testing has high clinical use for risk stratifying patients with known or suspected CAD, in patients after myocardial infarction, and in patients needing noncardiac surgery. Vasodilating agents are particularly advantageous in assessing post-myocardial infarction patients, allowing testing as soon as 2 days after the event. Like patients undergoing exercise stress testing, patients with normal perfusion images by pharmacological stress have a <1% annual incidence of cardiac events. The likelihood of an event increases with the extent and severity of perfusion abnormalities. However, it is important to consider clinical variables when using perfusion imaging for risk stratification, particularly in the presurgery patients. As with exercise testing, adjunct markers such as ST segment depression during testing, lung uptake of radiotracer (if thallium is used), and ventricular cavity dilatation add additional prognostic information to that available from the perfusion images alone. The aim of current research is to find better agents that are easier to use and that have fewer side effects. MRE-0470 is an experimental vasodilating agent that is more receptor selective than adenosine and promises a lower incidence of hypotension. Arbutamine more closely simulates exercise than dobutamine, and it can be administered by a closed-loop computerized delivery device. Work is also underway to look at novel uses of pharmacological stress agents, such as acquiring gated SPECT images during dobutamine infusion to enhance detection of myocardial viability. With increasing use of noninvasive testing in elderly patients and in patients with comorbidities that preclude adequate exercise, pharmacological stress testing has become an indispensable tool for radionuclide myocardial perfusion imaging studies. A good understanding of pharmacological stress testing is essential for performing high-quality nuclear cardiology

Noninvasive Measurement of Left Coronary Blood Flow Reserve by Transthoracic Doppler Echocardiography: Comparison with Doppler Guidewire Ultrasonography.

The development of new ultrasound instrumentation has made epicardial coronary artery blood flow imaging easier with the use of transthoracic coronary Doppler echocardiography (TCDE). This study was performed to investigate the accuracy of coronary blood flow reserve (CFR) measurement by TCDE. In 15 patients with ischemic heart disease in the absence of valvular disease or atrial fibrillation, coronary flow at rest and flow with hyperemia induced by intravenous dipyridamole infusion were recorded by TCDE and Doppler guidewire ultrasonography. The CFR was determined as the ratio of the maximum hyperemic diastolic time-averaged peak velocity to the velocity at rest in the proximal or distal left anterior descending coronary artery. It was found that the CFR of the left anterior descending coronary artery measured by TCDE was comparable in accuracy with CFR measured by invasive methods (r = 0.87, P < 0.0001, n = 15).

Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease: Results from the pilot phase of the Women’s Ischemia Syndrome Evaluation (WISE) Study

OBJECTIVESWe sought to develop and validate a definition of coronary microvascular dysfunction in women with chest pain and no significant epicardial obstruction based on adenosine-induced changes in coronary flow velocity (i.e., coronary velocity reserve).BACKGROUNDChest pain is frequently not caused by fixed obstructive coronary artery disease (CAD) of large vessels in women. Coronary microvascular dysfunction is an alternative mechanism of chest pain that is more prevalent in women and is associated with attenuated coronary volumetric flow augmentation in response to hyperemic stimuli (i.e., abnormal coronary flow reserve). However, traditional assessment of coronary volumetric flow reserve is time-consuming and not uniformly available.METHODSAs part of the Women’s Ischemia Syndrome Evaluation (WISE) study, 48 women with chest pain and normal coronary arteries or minimal coronary luminal irregularities (mean stenosis = 7%) underwent assessment of coronary blood flow reserve and coronary flow velocity reserve. Blood flow responses to intracoronary adenosine were measured using intracoronary Doppler ultrasonography and quantitative angiography.RESULTSCoronary volumetric flow reserve correlated with coronary velocity reserve (Pearson correlation = 0.87, p < 0.001). In 29 (60%) women with abnormal coronary microcirculation (mean coronary flow reserve = 1.84), adenosine increased coronary velocity by 89% (p < 0.001) but did not change coronary cross-sectional area. In 19 (40%) women with normal microcirculation (mean flow reserve = 3.24), adenosine increased coronary velocity and area by 179% (p < 0.001) and 17% (p < 0.001), respectively. A coronary velocity reserve threshold of 2.24 provided the best balance between sensitivity and specificity (90% and 89%, respectively) for the diagnosis of microvascular dysfunction. In addition, failure of the epicardial coronary to dilate at least 9% was found to be a sensitive (79%) and specific (79%) surrogate marker of microvascular dysfunction.CONCLUSIONSCoronary flow velocity response to intracoronary adenosine characterizes coronary microvascular function in women with chest pain in the absence of obstructive CAD. Attenuated epicardial coronary dilation response to adenosine may be a surrogate marker of microvascular dysfunction in women with chest pain and no obstructive CAD.

Hypertrophic Cardiomyopathy: MR Measurement of Coronary Blood Flow and Vasodilator Flow Reserve in Patients and Healthy Subjects

To evaluate coronary blood flow per gram of myocardial mass and vasodilator flow reserve in patients with hypertrophic cardiomyopathy (HCM) and in healthy subjects by using breath-hold velocity-encoded cine (VEC) magnetic resonance (MR) imaging. Twenty-nine patients with HCM and nine healthy volunteers were examined. Fast VEC MR images were obtained in an oblique imaging plane perpendicular to the coronary sinus before and after intravenous injection of dipyridamole (0.56 mg/kg). The products of mean velocity and cross-sectional area of the vessel were integrated to measure blood flow. Breath-hold cine MR images encompassing the entire left ventricle were acquired to quantify the left ventricular mass. In the basal state, the coronary blood flow per gram of myocardial mass was 0.74 mL/min/g +/- 0.23 in healthy subjects and 0.62 mL/min/g +/- 0.27 in patients with HCM. After administration of dipyridamole, coronary blood flow in patients with HCM increased to a level significantly less than that in healthy subjects (1.03 mL/min/g +/- 0.40 vs 2.14 mL/min/g +/- 0.51; P < .01), resulting in a severely depressed flow reserve ratio in patients with HCM compared with that in healthy subjects (1.72 +/- 0.49 vs 3.01 +/- 0.75; P < .01). Breath-hold VEC MR imaging is a noninvasive technique for evaluating coronary flow per gram of myocardial mass and coronary flow reserve.

Fast magnetic resonance imaging of the heart

Fast MR imaging techniques have multiple applications for evaluation of cardiac disease. Cine MRI and MR tagging have been shown to be highly accurate and reproducible in evaluating regional and global myocardial function. Segmented k-space cine MRI and echo-planar imaging (EPI) can considerably improve time efficiency and thereby the clinical utility of these techniques. Double IR fast spin-echo sequences enable breath-hold acquisition of T2 weighted MRI with good suppression of the blood signal. Myocardial perfusion can be assessed with fast dynamic MRI after administration of contrast media. Multi-shot EPI improves temporal resolution and also provides full coverage of the left ventricle. Substantial progress has been made in respiratory gated 3D coronary artery MR angiography with navigator echoes. The newer approaches for coronary arterial imaging including breath-hold three-dimensional segmented EPI and high resolution spiral MRI may further improve clinical usefulness of coronary MR angiography. Assessment of coronary blood flow and flow reserve with phase contrast MRI has the potential for the non-invasive evaluating of the presence and significance of stenosis in the native coronary artery and bypass grafts. Fast cardiac MRI may emerge as a cost effective modality for comprehensive assessments of both cardiac morphology, function, blood flow and perfusion.

Prevalence of Coronary Blood Flow Reserve Abnormalities Among Patients With Nonobstructive Coronary Artery Disease and Chest Pain

To determine the prevalence of abnormalities in endothelium-dependent and endothelium-independent coronary flow reserve among patients with non-obstructive coronary artery disease and chest pain. We studied endothelium-dependent (after infusion of 10(-6) M to 10(-4) M of acetylcholine) and endothelium-independent (after administration of 18 to 36 micrograms of adenosine) coronary flow reserve among patients with nonobstructive coronary artery disease and chest pain who were undergoing assessment at Mayo Clinic Rochester. Coronary blood flow was derived from coronary artery diameter assessed by quantitative angiography and Doppler flow velocities. The cohort consisted of 203 patients (158 female and 45 male patients), who ranged in age from 17 to 78 years (mean, 51). Most patients (92%) had at least one risk factor for atherosclerosis; a substantial proportion had undergone extensive cardiac and noncardiac evaluation. Whereas 41.5% of the patients had normal coronary flow reserve, 58.5% had an abnormal response: 11.3% an impaired response to adenosine (flow velocity ratio of 2.5 or less), 29.2% an impaired response to acetylcholine (flow reserve ratio of 1.5 or less), and 18% a combined abnormality. No correlation (r2 = 0.03) was noted between endothelium-dependent and endothelium-independent flow reserve. Most study patients with chest pain and nonobstructive coronary artery disease undergoing coronary vasomotor evaluation had risk factors for coronary artery disease and diverse abnormalities in endothelium-dependent or endothelium-independent coronary flow reserve (or both). These findings underscore the need for a comprehensive assessment.

Coronary Vascular Remodeling in Association With Endothelial Dysfunction

Vascular remodeling has been demonstrated in advanced and early coronary artery disease. Whereas the endothelium may play a role in the adaptive process of vascular remodeling, it is not known if this process occurs in association with changes in coronary blood flow reserve. Early coronary atherosclerosis is characterized by endothelial dysfunction which is manifested by an abnormal coronary blood flow in response to the endothelium-dependent vasodilator acetylcholine. This study was designed to test the hypothesis that coronary vascular remodeling occurs in association with coronary endothelial dysfunction early in the development of coronary atherosclerosis. Thirty-six patients found to have normal coronary angiograms or mild coronary artery disease were studied. Acetylcholine was infused into the left anterior descending artery. Patients were divided into 2 groups based on their coronary blood flow response to acetylcholine. Intravascular ultrasound measurements of the proximal left anterior descending diameter and area were obtained. Vessel diameter and area were measured at the external elastic membrane and indexed to body surface area. Vessel diameter and area were greater in patients with abnormal than normal responses to acetylcholine (5.2 ± 0.3 mm and 19.5 ± 0.9 mm 2 vs 3.9 ± 0.3 mm and 12.3 ± 1.0 mm 2; p <0.02, respectively). This difference persisted when measurements were indexed to body surface area. The current study suggests in vivo in humans that coronary vascular remodeling characterized by enlargement of the proximal coronary arteries occurs in association with endothelial dysfunction early in the course of coronary artery disease.

Effect of Ventricular Pacing on Coronary Blood Flow in Patients with Normal Coronary Arteries

Although ventricular pacing is thought to produce impairment of left ventricular function by altering the sequence of ventricular activation and AV dyssynchrony, little is known about the effect of ventricular pacing on coronary blood flow. We measured coronary blood flow and coronary flow reserve in the left anterior descending coronary artery during sinus rhythm, and during both atrial and ventricular pacing at a rate of 100 ppm in 14 patients with normal coronary arteries. The double product increased significantly during both types of pacing. Coronary arterial diameter during ventricular pacing significantly increased compared to that during both sinus rhythm and atrial pacing. Coronary flow velocity during ventricular pacing was significantly lower compared to that during both sinus rhythm and atrial pacing. Coronary blood flow increased significantly during atrial pacing (30.7% +/- 12.1%; P < 0.001), but not significantly during ventricular pacing (23.6% +/- 47.0%; P = ns). While coronary flow reserve during both atrial (3.9 +/- 1.3) and ventricular pacing (3.8 +/- 0.9) was lower compared to its value during sinus rhythm (4.5 +/- 1.5), the difference was not significant. There was a significant positive correlation between the coronary flow reserve during sinus rhythm and the increase of coronary blood flow during ventricular pacing (R2 = 0.78; P < 0.001). We concluded that an increase in coronary blood flow during ventricular pacing is not a common finding regardless of the increase in metabolic demand. The increase of coronary blood flow during ventricular pacing was less in patients with a reduced coronary flow reserve. These findings suggest that preservation of AV synchrony and the presence of a normal sequence of ventricular activation may play an important role in preserving coronary blood flow in this subset of patients.

Cardiac microvascular vasomotor response as a prognostic marker of left ventricular function in cardiac transplant recipients

T HE long-term survival of patients after heart transplantation is limited by the development of cardiac allograft vasculopathy (CAV).’ The lumina of the smaller intramyocardial branches are often occluded before those of the larger epicardial arteries and this results in small, multiple, stellate infarcts.’ To assess the degree to which transplant vascular sclerosis affects the resistance vessels, coronary blood flow measurement is useful. Several studies in transplant recipients suggest that resistance vessel function is altered at an early stage of the coronary disease process. 3,4 The left ventricular systolic function is relatively well preserved in patients without significant acute rejection5 but the importance of microvascular vasomotor (dys)function in the development of reduced left ventricular function has not been investigated. Therefore, it was the purpose of the present study to assess the relationship of coronary blood flow reserve (CFR) and subsequent changes in left ventricular systolic function to establish the clinical utility of coronary flow measurement to identify a distinct subset of patients in whom closer monitoring and aggressive risk factor modification may be indicated.

Coronary blood flow velocities during rotational atherectomy.

This study was designed to evaluate the alterations in doppler derived coronary blood flow velocities and flow reserve following rotational ablation. Changes in doppler derived coronary blood flow velocity variables have been valuable in assessing the physiological outcome following coronary balloon angioplasty. Rotational ablation's mechanism of plaque removal could alter distal vascular bed characteristics, and, as a result, intracoronary blood flow velocities and the coronary flow reserve. A 12-MHz doppler guidewire recorded intracoronary phasic velocities and coronary flow reserve (as assessed by the hyperemic response to adenosine [12-18 mcg intracoronary]) in 28 patients, before and after rotational ablation of 30 lesions. Adjunctive balloon angioplasty was performed in 27 of 28 patients (96%). Rotational ablation and adjunctive balloon angioplasty successfully reduced the lesion diameter (87 +/- 9% to 14 +/- 11%; P < 0.001). A significant increase in the mean distal average peak velocity (25 +/- 13 cm/sec, before; 47 +/- 22 cm/sec, after; P < 0.001), and decrease in the proximal to distal average peak velocity ratio, (2.1 +/- 1.3; to 1.2 +/- 0.4; P = 0.002) was recorded. The mean distal diastolic to systolic velocity ratio (before, 1.4 +/- 0.7; after, 1.6 +/- 0.8; P = 0.44) and the coronary flow reserve (before, 1.6 +/- 0.6; after, 1.5 +/- 0.5; P = 0.34) did not increase despite increases in distal velocities, following successful intervention. Doppler derived distal coronary blood flow velocities increased following rotational ablation and adjunctive balloon angioplasty, with resolution of transstenotic velocity gradient. Changes in distal phasic velocity pattern and coronary flow reserve, immediately after the intervention, were not useful in the assessment of the functional outcome and may be related to abnormalities in distal vascular bed vasoreactivity produced by rotational ablation.

Hypertension, left ventricular hypertrophy, and coronary flow reserve.

The increased independent risk for premature cardiovascular mortality related to left ventricular hypertrophy (LVH) may be attributed to a number of underlying pathophysiological alterations(1). Among the postulated mechanisms are: an intrinsic pathological defect inherent with the hypertrophied myocardium, per se; impaired ventricular pumping ability that may exacerbate decompensation; co-existent diseases of the left ventricle (e.g., occlusive epicardial artery atherosclerosis, exogenous obesity, diabetes mellitus); increased myocardial irritability that predisposes to sudden cardiac death; co-existing pharmacological therapy; and impaired coronary hemodynamics including coronary blood flow reserve. A number of current investigations are focusing on the possibility that reduced coronary blood flow and flow reserve predispose the hypertensive patient with LVH to premature mortality. Those factors that may participate in potentially lethal ischemia include: reduced basal coronary blood flow and coronary flow reserve; increased coronary vascular resistance and minimal coronary vascular resistance; reduced vasodilating capability of the hypertensive coronary arterioles (e.g., from reduced endothelial synthesis of nitric oxide and other substances); and altered blood viscosity in the coronary microcirculation.KeywordsLeft Ventricular HypertrophyLeft Ventricular MassCoronary Flow ReserveCoronary Blood FlowCoronary Vascular ResistanceThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Measurement of coronary blood flow and flow reserve using magnetic resonance imaging.

It was the purpose of this study to demonstrate the feasibility of performing coronary artery flow and coronary flow reserve (CFR) measurements in normal human volunteers using a magnetic resonance (MR) phase contrast technique. Coronary flow rate, flow velocity, peak flow and CFR were determined at rest and during pharmacologically induced hyperemia in 10 healthy volunteers. The flow measurements were obtained during a single breath-hold by using a fast, prospectively gated, segmented k-space gradient-echo phase contrast acquisition with view sharing (FASTCARD PC) that was modified to improve sampling of the diastolic flow. Data were processed using the standard phase difference (PD) processing techniques as well as a new complex difference (CD) flow measurement method intended to improve the accuracy of flow measurements in small vessels. Mean hyperemic flow velocity (40 +/- 16 cm/s) and blood flow (3.9 +/- 1.5 ml/s) rates differed significantly from resting velocity (13 +/- 6.6 cm/s) and flow (1.1 +/- 0.4 ml/s) measurements (p < 0.0001). PD methods consistently measured larger flow rates at rest (24% larger, p < 0.0005) and stress (29% larger, p < 0.0001). CFR, calculated as the ratio of the mean PD flows (4.7 +/- 2.8), was higher than CFR calculated as the ratio of mean CD flows (4.2 +/- 1.8); however, the differences did not reach statistical significance (p = 0.07). Flow measurements performed in adjacent slices of the same vessel correlated well (r = 0.88). Coronary flow and CFR measurements using the MR techniques are feasible and are similar to those reported in the literature for healthy volunteers.

Usefulness of dipyridamole transesophageal echocardiography in the evaluation of myocardial ischemia and coronary artery flow.

High-dose dipyridamole transesophageal stress echocardiography has recently been proposed as a useful and safe method to assess myocardial ischemia in patients with poor transthoracic acoustic window. It has also been shown that transesophageal echocardiography (TEE) allows the study of coronary blood flow reserve (CBFR) in the left anterior descending artery (LAD). The aim of our study was to assess whether the morphologic information and pathophysiologic data on CBFR and myocardial ischemia can be collected by a single stress TEE without comprimizing its feasibility, safety and accuracy. We studied, 29 patient with known or suspected CAD (previous myocardial infarction or angina) (Group A), and as a control group, we studied 11 patients with mitral disease or mitral prostheses (Group B). All patients underwent the coronary angiography. None of Group B patients showed significant coronary artery stenosis (> 70%). In baseline conditions left ventricular wall motion and LAD coronary blood flow velocity (CBFV) were also evaluated. The following CBFV parameters were measured: maximal diastolic velocity (MaxDV), mean diastolic velocity (MnDV), maximal systolic velocity (MaxSV), mean systolic velocity (MnSV). The ratios of dipyridamole to rest maximal and o mean to diastolic velocities (MaxDV-Dip/Max DV-rest; MnDv-Dip/MnDV-rest) were measured as indexes of CBFR. No side effects were observed and the test could be completed in all patients (feasibility 100%). Wall motion analysis was adequate in all patients (feasibility 100%). Comparison between wall motion analysis was obtained and angiographic findings shown that the overall sensitivity and specificity of TEE were 84% and 93% respectively. Sensitivity for one, two and three vessel disease was 60%, 70% and 100%, respectively. LAD CBFV was adequately recorded in 85% of patients. CBFR parameters showed a significant difference between the two groups (Max DV-Dip/Max DV-rest: 1.67 +/- 0.7 vs. 2.73 +/- 0.6, P < 0.001); comparison between Group B patients and those of Group A with angiographically documented LAD stenosis showed a statistically significant difference in CBFR parameters (MaxDV-Dip/MnDV-rest, 2.73 +/- 0.6 vs. 1.65 +/- 0.7, P < 0.001, MnDV-Dip/MnDV-rest, 2.56 +/- 0.5 vs. 1.69 +/- 0.6 < 0.001). We conclude that transesophageal stress echocardiography is a useful method to study CAD and that it is possible to assess both morphologic and pathophysiologic information during a single examination.

Blunted coronary reserve in myotonic dystrophy. An early and gene-related phenomenon.

In myotonic dystrophy (DM), striated muscle is involved in relation to the size of the DNA mutation. Smooth muscle may be similarly impaired at the level of the urinary and digestive apparatus and possibly at the level of small vessels, since microangiopathy has been described in the iris and digital capillaries. Our purpose was to study the function of the myocardial microvasculature in relation to the size of the mutation in DM patients without clinical cardiac involvement and with normal left ventricular dimensions and function and normal large coronary arteries. In 6 control subjects and 10 DM patients, we investigated the coronary blood flow reserve using positron emission tomography with 15O-labeled water. Global and regional flow reserves were obtained from myocardial regions of interest manually drawn on a static FDG image encompassing, respectively, the whole left ventricle and the anterior, septal, and lateral walls. The DNA mutation size was determined on circulating lymphocytes in each DM patient. Compared with control subjects, DM patients had decreased global (2.39 +/- 0.39 versus 4.00 +/- 0.67, P = .00003) and regional (anterior, 2.39 +/- 0.64 versus 3.87 +/- 0.92, P = .002; septal, 2.60 +/- 0.48 versus 4.00 +/- 0.70, P = .0003; lateral, 2.26 +/- 0.58 versus 4.16 +/- 1.11, P = .0005) coronary reserves. In DM patients, the coronary reserve correlated strongly and inversely with the DNA mutation size (r = -.77, P = .009). The study demonstrated that global and regional coronary reserves are impaired, in relation to the DNA mutation size, in symptom-free DM patients with normal ventricular dimensions and function and normal large coronary vessels. We suggest that a gene-related blunted coronary reserve resulting from an impairment of vascular smooth muscle is an early component of DM cardiomyopathy.

Failure to demonstrate myocardial ischaemia in patients with angina and normal coronary arteries. Evaluation by continuous coronary sinus pH monitoring and lactate metabolism.

Whether myocardial ischaemia is the mechanism underlying chest pain in patients with angina and normal coronary arteriograms is controversial. We sought to detect the presence of transient myocardial ischaemia using continuous monitoring of coronary sinus blood pH during atrial pacing. We studied 14 patients (eight women, six men, mean age 51 +/- 3 years) with typical exertional angina and normal coronary arteriograms and nine patients with coronary artery disease (two men, seven women, mean age 61 +/- 7 years). Of the 14 patients with normal coronary arteries, eight had a reduced coronary blood flow reserve (< 2.5-fold increase), 11 had an ischaemic-appearing response to exercise testing, six had reversible perfusion detects on exercise thallium scans and one had resting left bundle branch block. All patients underwent continuous pH monitoring of coronary sinus blood at rest and during incremental atrial pacing (up to 160 bpm). Coronary sinus oxygen saturation and myocardial lactate extraction ratio were also evaluated at rest and at peak pacing. Eleven patients with angina and normal coronary arteries and eight with coronary artery disease had angina during pacing. Both patients with angina and normal coronary arteries (n = 13) and patients with coronary artery disease (n = 9) showed a fall in coronary sinus pH (-0.02 +/- 0.02 vs -0.11 +/- 0.03 pH units, respectively, P < 0.01). Coronary sinus oxygen saturation expressed as a percentage dropped by 19 +/- 6% in patients with coronary artery disease and by 6 +/- 2% in patients with angina and normal coronary arteriograms (P < 0.05). Myocardial lactate extraction ratio decreased from 33 +/- 6% to -1.4 +/- 4% in patients with coronary artery disease and from 23 +/- 8% to 20 +/- 8% in those with angina and normal coronary arteriograms. Three patients with angina and normal coronary arteries had a drop in coronary sinus pH > 0.02 pH units (-0.043 +/- 0.006 pH units) and in coronary sinus oxygen saturation > 8% (16 +/- 3%) consistent with myocardial ischaemia. Despite severe chest pain and reduced coronary flow reserve after pacing, most patients with angina and normal coronary arteriograms do not show metabolic evidence of myocardial ischaemia.

Second harmonic imaging of an intravenously administered echocardiographic contrast agent: Visualization of coronary arteries and measurement of coronary blood flow

Objectives. This study sought to evaluate the potential of second harmonic contrast echocardiography to assess coronary vasculature.Background. Newer transpulmonary ultrasound contrast agents capable of resonance phenomena detected by harmonic imaging may theoretically be able to demonstrate blood flow in the myocardium.Methods. Transthoracic B-mode images and Doppler were obtained using a prototype second harmonic ultrasound system after femoral vein injection of AFO145 (10 to 40 mg) in 13 closed chest dogs (mean weight 25.6 kg). Coronary Doppler flow was simultaneously invasively measured using an intracoronary flow wire and visually compared with transthoracic Doppler flow. “Noninvasive” coronary vasodilator reserve was determined by measuring the ratio of the Doppler time velocity integral after adenosine to the baseline value and compared with the “invasive” intracoronary determination.Results. Harmonic imaging showed heterogeneous opacification of the myocardium characterized by linear branching structures consistent with intramyocardial coronary arteries, which were not clearly visible during conventional ultrasound imaging. In nine dogs, transthoracic Doppler was performed, and characteristic coronary Doppler flow was observed, identical to the simultaneously observed intracoronary Doppler flow. Intracoronary adenosine (120 to 150 μg) equally increased intracoronary and transthoracic Doppler flow velocities. The calculated “noninvasive” and “invasive” coronary vasodilator reserve ratios were similar ([mean ± SD] 3.3 ± 1.0 and 3.6 ± 1.2, p = NS), with excellent correlation (r = 0.95, p = 0.0012).Conclusions. These findings indicate that noninvasive assessment of intramyocardial coronary vasculature and measurement of coronary blood flow reserve are possible using second harmonic contrast echocardiography.