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Background: In patients with asymptomatic aortic stenosis (AS), exercise stress echocardiography (ESE) provides additional prognostic information beyond baseline. The coronary flow velocity reserve (CFVR) is impaired in AS, but its link with exertion is unknown in this setting. The aim of this study was to test the hypothesis that CFVR could predict exercise capacity and abnormal exercise test results in AS., Methods: Noninvasive CFVR and symptom-limited semisupine ESE were prospectively performed the same day in 43 patients with asymptomatic isolated severe AS (mean age, 68.5 ± 11 years; 26% women; mean aortic valve area, 0.8 ± 0.16 cm 2 ; mean left ventricular ejection fraction, 70 ± 7%). CFVR was performed in the distal part of the left anterior descending coronary artery using intravenous adenosine infusion (140 μg/kg/min over 2 min), and ESE was performed at an initial workload of 25 W with a 20- to 25-W increase at 2-min intervals. An abnormal result on ESE was defined as onset of symptoms at <75% of maximum predicted workload, electrocardiographic ST-segment depression ≥2 mm during exercise, increase of systolic blood pressure < 20 mm Hg or decrease in blood pressure, and complex ventricular arrhythmia. Seventeen patients with isolated severe asymptomatic AS, unable to exercise because of extracardiac conditions, served as a comparative group., Results: Resting, hyperemic left anterior descending coronary artery flow velocity and CFVR (2.45 ± 0.8 vs 2.4 ± 0.8) were similar between the group unable to perform ESE and the ESE group (P = NS for all). Compared with patients with normal results on ESE, those with abnormal results on ESE (n = 22) were older, had higher E/e' ratios, had higher resting left anterior descending coronary artery flow velocities (39 ± 12 vs 31 ± 8 cm/sec), and had lower CFVR (2.01 ± 0.3 vs 2.85 ± 0.7; P < .01 for all). Furthermore, CFVR was significantly correlated with age, changes in transvalvular pressure gradient and left ventricular ejection fraction with exercise, workload (in watts), and exercise duration (P < .05 for all). After adjusting for other variables, CFVR remained independently correlated with exercise duration, workload, and abnormal results on ESE (P < .01 for all). On receiver operating characteristic curve analysis, CFVR < 2.3 was the best cutoff to predict abnormal results on ESE (area under the curve = 0.88 ± 0.06, P < .01)., Conclusions: In patients with asymptomatic severe AS, noninvasive CFVR is correlated with exercise duration and workload, and low CFVR predicts abnormal results on ESE with good accuracy., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary flow reserve (CFR) is progressively impaired with aortic stenosis (AS) severity. However, there is a broad range of CFR in patients with severe AS, and the factors responsible for this variability are weakly characterized. The aim of this study was to assess the correlates of noninvasive CFR in patients with severe AS (≤1 cm(2) or ≤0.6 cm(2)/m(2)) and preserved left ventricular (LV) ejection fractions (LVEFs) (>50%)., Methods: Sixty-six consecutive patients (mean age, 74 ± 11 years; 31 women; mean LVEF, 69 ± 10%) with isolated severe AS (mean, 0.75 ± 0.2 cm(2) and 0.42 ± 0.1 cm(2)/m(2)), without coronary artery disease, underwent prospectively Doppler transthoracic echocardiography including CFR measurement in the distal part of the left anterior descending coronary artery (LAD) with intravenous adenosine infusion (140 μg/kg/min over 2 min). CFR was defined as hyperemic peak LAD flow velocity divided by baseline flow velocity. Twenty controls matched for age and gender served as a comparative group. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) was also assessed., Results: Compared with controls, patients with AS had higher baseline LAD flow velocities (36 ± 11 vs 27 ± 6 cm/sec, P < 0.01), lower hyperemic LAD flow velocities (80 ± 20 vs 89 ± 18 cm/sec, P = .09), and consequently lower CFR (2.3 ± 0.7 vs 3.3 ± 0.7, P < .01). In patients with AS, there were significant inverse correlations between CFR and age, E/e', indexed LV mass, NT-proBNP, pulmonary artery systolic pressure (PASP), baseline LV rate-pressure product, heart rate, and indexed left atrial volume and a significant positive correlation between CFR and LVEF (all P values < .05). Furthermore, compared with patients with asymptomatic AS (n = 22), those with symptomatic AS had more severely impaired CFR (2.15 ± 0.6 vs 2.7 ± 0.65), and higher NT-proBNP values (all P values < .05). In multivariate analysis, NT-proBNP, PASP, and LV rate-pressure product were the main independent correlates of CFR (all P values ≤ .01), and PASP was independently predicted by E/e' and indexed left atrial volume (all P values < .01)., Conclusions: In patients with severe AS and preserved LVEFs, there is a relatively broad range of CFR values. CFR is more severely impaired in patients with symptomatic AS and is mainly linked with NT-proBNP, a surrogate of increased LV wall stress, workload as measured by LV rate-pressure product, and PASP., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Objective: To assess the relationship between leukocyte count, non invasive coronary flow reserve (CFR), left ventricular systolic function, and in-hospital adverse events in acute anterior myocardial infarction (AMI) treated by primary angioplasty., Methods: Leukocyte count at admission and within 24h after angioplasty, and differential count at admission were obtained in 72 consecutive patients with a first AMI (mean age 56±12 years) successfully treated by primary angioplasty. Transthoracic Doppler echocardiography was performed within 24h after angioplasty and 3 months later to assess the CFR (using intravenous adenosine), in the left anterior descending artery (LAD), left ventricular ejection fraction (LVEF) and the wall motion score index using the nine segments assigned to the LAD territory (WMSi-lad). In hospital events were defined as death, heart failure (Killip≥2) and reinfarction., Results: Leukocyte count was higher before and after angioplasty in patients with impaired acute CFR (<1.7), when compared to patients without such impairment (P≤0.01), and a significant correlation was found between CFR and leukocyte, neutrophil and monocyte count (P<0.05). Leukocyte (before and after angioplasty), and neutrophil count, were lower in patients with recovery of global and regional LV function (P<0.05). A significant correlation was found between leukocyte count before and after angioplasty, and, initial and follow-up LVEF, and WMSi-lad (all, P≤0.01). Leukocyte (before and after angioplasty) and monocyte count were higher in patients with in-hospital events (n=14), by comparison to patients without events (all, P<0.01). In multivariate analysis, leukocyte count after angioplasty was an independent predictor of CFR, and in-hospital events, and neutrophil count of WMSi-lad at follow-up (all, P<0.05)., Conclusion: In the first AMI treated successfully by primary angioplasty, leukocyte count is inversely correlated to CFR, and global and regional LV systolic function at follow-up. These links are higher after than before reperfusion. And, leukocyte count after angioplasty is an independent predictor of in-hospital adverse events., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Aims: Prognostic value of transthoracic coronary flow reserve (T-CFR) is not established in patients with left anterior descending artery (LAD) stenosis of intermediate severity. Objective is to determine the prognosis value of T-CFR>2 in medically treated patients with angiographically intermediate [50-70% QCA (quantitative coronary angiography)] proximal LAD stenosis., Methods and Results: Among 110 consecutive patients with intermediate LAD stenosis who underwent prospectively T-CFR in the distal part of the LAD after intravenous administration of adenosine to assess the functional significance of the stenosis, 80 patients had T-CFR>2 and were treated medically without revascularization (Group 1). Among the 30 patients who had T-CFR<2, an additional dobutamine stress echocardiography (DSE) was performed: 15 had a negative DSE; were treated medically and served as a comparative group (Group 2), and 15 had a positive DSE; underwent LAD revascularization, and were excluded from further analysis. All patients completed follow-up (16+/-10 months). During the follow-up period (range 6-45 months), 76 patients (95%) remained free of death or LAD-related event in Group 1, vs. 12 patients (80%) in Group 2. By Kaplan-Meier method, at 30 months the per cent estimated survival free from death or target vessel-related events was 92+/-4% in Group 1 and 44+/-22% in Group 2 (P<0.01). By multivariate analysis, T-CFR remained the only independent predictor of death or LAD-related events., Conclusion: In patients with proximal LAD stenosis of intermediate severity and T-CFR>2, deferral of revascularization is associated with low event rate.

The clinical features of tako-tsubo cardiomyopathy or transient left apical ballooning syndrome (LABS) have been clearly described, but the mechanisms are still unknown. Our objective was to prospectively assess coronary microcirculation at the acute phase of LABS and after functional recovery, using Doppler transthoracic echocardiography-coronary flow reserve (CFR). Twelve consecutive patients (11 women, mean age 68 +/- 10 years) satisfying the criteria for LABS underwent Doppler transthoracic echocardiography-CFR in the distal part of the left anterior descending coronary artery, using intravenous adenosine infusion (0.14 mg/kg/min over 2 minutes) at the acute phase and 25 +/- 3 days later. CFR was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. Wall-motion score (WMS) was calculated using the 16-segment model during the same echocardiographic examination (normal WMS = 16). Doppler transthoracic echocardiography-CFR increased between the two examinations from 2.2 +/- 0.4 at the acute phase to 2.9 +/- 0.3 (P < .01), whereas WMS decreased (from 31 +/- 6 at the acute phase to 16.5 +/- 0.8, delta WMS = -14.6 +/- 6, P < .01). All patients exhibited an increase of CFR between the two tests (delta CFR = 0.73 +/- 0.39, range: 0.3-1.6). A significant correlation was observed between delta CFR and delta WMS (r = -0.89, P < .01). In conclusion, serial noninvasive CFR measurements performed in LABS suggested transient microcirculatory impairment during the acute phase of the syndrome. The wall-motion improvement parallel to the dynamic improvement of the microcirculation suggests a role of coronary microcirculatory damage in the pathogenesis of acute and transient wall-motion abnormalities in LABS.

Objective: We sought to compare coronary flow velocity reserve (CFVR) with adenosine and dobutamine in patients scheduled for noninvasive evaluation of coronary artery disease., Background: Assessment of CFVR in the distal part of the left anterior descending coronary artery (LAD) by Doppler transthoracic echocardiography (TTE) is usually performed with adenosine in various settings. CFVR can also be determined during dobutamine stress echocardiography (DSE), but it has not been established whether TTE CFVR with dobutamine is equivalent to CFVR with adenosine., Methods: In all, 47 consecutive stable patients in sinus rhythm (28 men, 64 +/- 12 years, left ventricular ejection fraction 55 +/- 5%) were prospectively studied. Coronary flow velocity was measured in the distal part of the LAD by TTE, at rest and during continuous infusion of 0.14 mg/kg/min of adenosine over 2 minutes, and during DSE performed immediately after the adenosine test, using a multifrequency transducer, on a modified parasternal view. CFVR with adenosine was calculated as hyperemic to basal peak flow velocity. CFVR with DSE was obtained by calculating peak diastolic flow velocity divided by baseline diastolic flow velocity., Results: Adequate recording of CFVR with adenosine and dobutamine was possible in 43 (91%) and 41 (87%) patients, respectively. CFVR was 2.5 +/- 0.7 with adenosine compared with 2.4 +/- 0.7 with dobutamine (P = .7). A good linear correlation was observed between the two tests (r = 0.81, P < .0001). In patients with dobutamine-induced wall-motion abnormalities in the LAD territory (n = 8), CFVR was similar during dobutamine and adenosine infusion (1.6 +/- 0.3 vs 1.5 +/- 0.2, respectively, P = .7). Coronary angiography was available in 12 patients (LAD stenosis: 55 +/- 10% quantitative coronary angiography, with a range from 40%-75%). The correlation between CFVR values was also good in this subgroup of patients (r = 0.87, P < .0001)., Conclusion: TTE CFVR with dobutamine is comparable to CFVR with adenosine in patients with a wide range of LAD diseases. Dobutamine could be a good alternative to adenosine for TTE CFVR assessment, particularly in patients with a contraindication to adenosine or scheduled for DSE.

The measurement of coronary reserve flow by transthoracic echocardiography of the left anterior descending and the posterior interventricular artery is a new non-invasive reproducible and attractive method which can be performed at the bedside with the proviso of a specific learning curve. The potential value is great: detection of significant (> 70%) coronary stenosis, coronary occlusion, post-angioplasty follow-up, evaluation of intermediate stenoses, coupling with stress echo, reperfusion studies, no reflow detection, post-infarction viability, coronary bypass patency and studies of microcirculation.

Non invasive evaluation of coronary flow and flow reserve by using transthoracic echocardiography is a promising method for evaluating coronary disease. Left anterior descending and right posterior descending coronary flow are accessible in the majority of patients. This technique is useful in various settings: detection of coronary artery stenosis, coronary occlusion, follow up after percutaneous coronary intervention, evaluation of the significance of coronary stenosis of intermediate severity, evaluation of the microcirculation, study of reperfusion and no reflow in the acute phase of myocardial infarction, evaluation of bypass grafts, improvement of the diagnostic accuracy during stress echocardiography. After a period of training, it's possible to change an old concept, formerly not easily accessible in clinical practice, into a useful and modern tool for evaluating coronary artery disease.

Abstract: Background: After acute myocardial infarction (MI) coronary microvascular impairment and reduced exercise capacity are both determinant of prognosis. Objective: We tested whether non-invasive coronary flow reserve (CFR) performed after MI predicts post-MI exercise capacity (EC). Methods: Fifty consecutive patients (pts) (mean age 56.5±11years, 30% women) with a first reperfused ST-elevation anterior MI, and sustained TIMI 3 flow after mechanical reperfusion, underwent prospectively non-invasive CFR in the distal part of the left anterior descending artery (LAD), using intravenous adenosine infusion (0.14mg/kg per minute, within 2min), within 24h after successful primary coronary angioplasty (CFR 1), and 4±1.6months later after a period of convalescence and a cardiac rehabilitation program (CFR 2). CFR was defined as peak hyperaemic LAD flow velocity divided by baseline flow velocity. All pts also underwent semi-supine exercise stress echocardiography (ESE) the same day of CFR 2. ESE was performed at an initial workload of 25–30watts with a 20watts increase at 2-minute intervals. Beta-blockers were withheld 24h before ESE. Results: The mean CFR 2 increased significantly when compared to CFR 1 (2.9±0.65 versus 1.9±0.4, P <0.01). During ESE, percentage of maximal predict heart rate achieved was 82±12%, maximal workload 95±30watts, exercise duration 486±155s, the ratio of double product 3.1±0.8, and EC 5.8±1.1 metabolic equivalents. No ischemia was induced during ESE in all pts, and the degree of mitral regurgitation did not differ significantly between rest and exercise. CFR 2 was significantly correlated to all indices related to EC (all, P <0.01), whereas CFR 1 was correlated to LV systolic function at follow-up (P <0.05) but not to EC. In multivariate analysis including age, sex, and body mass index, CFR 2 remained an independent predictor of EC (P <0.01). Conclusion: Contrarily to acute CFR, CFR at follow-up is an independent predictor of EC after reperfused anterior MI. This suggests that the improvement of the coronary microcirculation is closely linked to the physical aptitude after MI. [Copyright &y& Elsevier]