Frequency of drug-induced valvular heart disease in patients previously exposd to benfluorex: a multicentre prospective study.

AIMS: The epidemiologic link between benfluorex use and an increased global frequency of left heart valve regurgitation has been well documented. However, no data linking previous drug exposure to the frequency of diagnosis of drug-induced valvular heart disease (DI-VHD) are available. The present study was conducted to address this issue. METHODS AND RESULTS: This echocardiography reader-blinded, controlled study conducted in 10 centres between February 2010 and February 2012 prospectively included 835 subjects previously exposed to benfluorex referred by primary care physicians for echocardiography. Based on blinded off-line analysis, echocardiography findings were classified as: (i) DI-VHD⁺ for patients with an echocardiographic diagnosis of DI-VHD, (ii) inconclusive, and (iii) DI-VHD⁻ for patients without signs of DI-VHD. Fifty-seven (6.8%) patients exposed to benfluorex were classified as DI-VHD⁺, 733 (87.8%) patients were classified as DI-VHD⁻, and 45 (5.4%) were classified as inconclusive. Mitral and aortic DI-VHD were reported in 43 patients (5.1%) and 30 (3.6%) patients, respectively. Longer duration of exposure, female gender, smoking, and lower BMI were independently associated with a diagnosis of DI-VHD. Good inter-observer reproducibility was observed for the echocardiography classification (Kappa = 0.83, P < 0.00001). CONCLUSIONS: About 7% of patients without a history of heart valve disease previously exposed to benfluorex present echocardiography features of DI-VHD. Further studies are needed to study the natural history of DI-VHD and to identify risk factors for the development of drug-induced valve lesions.

Increased risk of left heart valve regurgitation associated with benfluorex use in patients with diabetes mellitus: a multicenter study.

BACKGROUND: Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least 3 months and in diabetic control subjects never exposed to the drug. METHODS AND RESULTS: This reader-blinded, controlled study conducted in 10 centers in France between February 2010 and September 2011 prospectively included 376 diabetic subjects previously exposed to benfluorex who were referred by primary care physicians for echocardiography and 376 diabetic control subjects. Through the use of propensity scores, 293 patients and 293 control subjects were matched for age, sex, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The main outcome measure was the frequency of mild or greater left heart valve regurgitations. In the matched sample, the frequency and relative risk (odds ratio) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared with control subjects: 31.0% versus 12.9% (odds ratio, 3.55; 95% confidence interval, 2.03-6.21) for aortic and/or mitral regurgitation, 19.8% versus 4.7% (odds ratio, 5.29; 95% confidence interval, 2.46-11.4) for aortic regurgitation, and 19.4% versus 9.6% (odds ratio, 2.38; 95% confidence interval, 1.27-4.45) for mitral regurgitation. CONCLUSIONS: Our results indicate that the use of benfluorex is associated with a significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research.

Assessment of left ventricular twist mechanics in Tako-tsubo cardiomyopathy by two-dimensional speckle-tracking echocardiography.

AIMS: To assess left ventricular (LV) twist mechanics in patients with Tako-tsubo cardiomyopathy (TTC). METHODS AND RESULTS: Two-dimensional strain and LV twist by speckle-tracking echocardiography was performed in 17 consecutive patients with typical TTC according to the Mayo clinic criteria [78 ± 8 years, 88% women, and mean left ventricular ejection fraction (LVEF) 45 ± 10%], at the acute phase (within 24 h after admission) and after recovery (1 month later). Seventeen control (C) patients matched for age and sex (mean LVEF 70 ± 7%), and 17 patients with acute anterior myocardial infarction (MI) treated by successful primary angioplasty 24 h before, matched for LVEF, age, and sex, were compared with TTC patients. LV twist was assessed using the parasternal basal and apical short-axis planes, and defined as the net difference in degrees of apical (Ar) and basal rotation (Br). Peak systolic and early diastolic, apical (As and Ad) and basal (Bs and Bd) rotation rate, and LV twisting rate (TR) and untwisting rate (UR) (in °/s) were derived from rotational and twist curves. The time sequences were normalized to the percentage of systolic duration. At the acute phase, Ar, As, Ad, Bs, LV twist (10 ± 9° vs. 23 ± 6°), LV TR, and LV UR were significantly impaired in patients with TTC when compared with controls (all, P < 0.05). Patients with MI displayed intermediate values (P = NS vs. TTC, and P < 0.05 vs. C). However, in the subgroup of patients with electrocardiogram ST-segment elevation at presentation (n = 12 TTC and 17 MI), several LV twist mechanics parameters were significantly reduced in TTC patients when compared with MI patients, LV twist, and LV TR being the most significant factors (all, P≤ 0.01). Abnormal reversed Ar (clockwise when seen from the apex) was seen in three patients (18%) with TTC vs. none in the other groups. A significant correlation between LV twist and LVEF, LV volumes, wall motion score index, and plasma NT-pro BNP was observed in the TTC group (all, P < 0.05). At follow-up, LV twist mechanics improved significantly in TTC patients (all, P < 0.05 vs. acute phase), who had final values similar to C (all, P = NS), whereas the magnitude of improvement was lower in MI patients (P ≤ 0.05 vs. TTC). CONCLUSION: LV twist mechanics is significantly impaired in patients with TTC mainly due to a severe reduction in apical function and is entirely reversible. Furthermore, in the subgroup of patients with ST-segment elevation, the early post-admission evaluation of LV twist mechanics is more severely impaired in TTC when compared with MI.

Non-invasive coronary flow reserve after successful primary angioplasty for acute anterior myocardial infarction is an independent predictor of left ventricular adverse remodelling.

AIMS: To assess the usefulness of non-invasive coronary flow reserve (CFR) to predict left ventricular adverse remodelling (LVR) after ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Sixty-five consecutive patients (mean age 58 +/- 13 years, 24 women) with a first anterior STEMI, underwent prospectively CFR in the distal part of the left anterior descending artery (LAD), using intravenous adenosine infusion (0.14 mg/kg/min, within 2 min), and a standard echocardiography during the same exam, performed within 24 h after successful primary coronary angioplasty, and 6 months later, while the patients were in stable haemodynamic situation. CFR was defined as the peak hyperaemic LAD flow velocity divided by the baseline flow velocity. LV end-systolic volume (ESV) and end-diastolic volume (EDV), and LV ejection fraction (LVEF) were measured using the biplane Simpson's rule. LVR was defined as an absolute increase of ESV > or =15%. Compared with patients without LVR, patients with LVR (n = 18) had higher peak troponin T levels, wall motion score (WMS), a worse initial angiographic TIMI flow grade, and less improved electrocardiographic ST-segment resolution (all P < 0.05), and lower CFR (1.43 +/- 0.2 vs. 1.97 +/- 0.5, P < 0.01). At 6 months, patients with LVR had higher WMS, ESV, EDV, and lower LVEF compared with patients without LVR (all P < 0.01). Furthermore, acute CFR was significantly correlated to the 6-month LVEF and ESV, and to change of LVEF and ESV (all P < 0.01). In the multivariate analysis, acute CFR and initial angiographic TIMI flow grade were the independent predictors of LVR (all P < or = 0.01). Receiver-operating characteristic curve analysis demonstrated that a cut-off value of 1.7 for CFR yields a sensitivity of 100% and a specificity of 62% to predict LVR at follow-up (P < 0.001, area under the curve 0.82). CONCLUSION: Non-invasive CFR is an independent predictor of LVR after successful primary angioplasty of anterior STEMI.

Usefulness of Noninvasive Myocardial Work to Predict Left Ventricular Recovery and Acute Complications after Acute Anterior Myocardial Infarction Treated by Percutaneous Coronary Intervention.

BACKGROUND: Predicting left ventricular recovery (LVR) after acute ST-elevation myocardial infarction (STEMI) is challenging and of prognostic importance. Our objective was to evaluate the usefulness of noninvasive myocardial work (MW), a new index of global and regional myocardial performance, to predict LVR and in-hospital complications after STEMI. METHODS: Ninety-three patients with anterior STEMI (mean age, 59 ± 12 years) treated by percutaneous coronary intervention (PCI) were prospectively enrolled and underwent a transthoracic Doppler echocardiography within 24-48 hours after PCI and a median of 92 days at follow-up. Myocardial work is derived from the strain-pressure relation, integrating in its calculation the noninvasive arterial pressure. Segmental LVR was defined as a normalization of wall motion abnormalities of the affected segments and global recovery as an absolute improvement of left ventricular ejection fraction (LVEF) > 5% in patients with baseline LVEF ≤ 50%. In-hospital complications were defined as a composite of death, reinfarction, heart failure, and LV apical thrombus. RESULTS: Segmental MW was impaired in infarct segments, more severely in nonrecovering versus recovering segments (P < .01). Furthermore, global constructive MW was significantly correlated with follow-up LVEF (r = 0.58) and global longitudinal strain (r = -0.67; all P < .01). Constructive MW was the best index to predict segmental (P < .01 vs MW index, MW efficiency, and wasted work) and global recovery (P < .05 vs global longitudinal strain) with an independent association (odds ratio = 1.17, 95% CI, 1.13-1.20, and odds ratio = 1.43, 95% CI, 1.18-1.68, respectively; all P < .001). Moreover, global constructive MW was more severely impaired in patients with in-hospital complications (n = 16; P < .01). CONCLUSIONS: In patients with anterior STEMI treated by PCI, constructive MW is an independent predictor of segmental and global LVR and is significantly impaired in patients with in-hospital complications.

Transient impairment of coronary flow reserve in tako-tsubo cardiomyopathy is related to left ventricular systolic parameters.

AIMS: Recent studies suggest that coronary flow reserve (CFR) is transiently impaired in tako-tsubo cardiomyopathy (TTC). Mechanisms by which such impairment occurs are still unknown. To assess the relationship between CFR obtained by transthoracic Doppler echocardiography (TDE) and parameters of left ventricular (LV) performance in patients with TTC. METHODS AND RESULTS: A total of 20 consecutive patients in sinus rhythm, with TTC (mean age 70+/-9 years, 19 women) underwent serial evaluation of TDE-CFR, in the distal part of the left anterior descending coronary artery (LAD), at the acute phase and after recovery using intravenous adenosine infusion (140 microg/kg/min over 2 min). CFR was calculated as hyperaemic to basal mean diastolic coronary flow velocity (CFV). Average of the septal and lateral mitral annulus early diastolic (Ea) and systolic (Sa) tissue velocity, early (E) and late (A) diastolic transmitral velocity, the ratio E/Ea, wall motion score (WMS, 16 segment model), LV end-systolic volume index (ESV/m(2)) and LV end-diastolic volume index (EDV/m(2), biplane-Simpson method) were serially measured by TDE. Basal CFV, LV mass index and haemodynamics parameters did not differ between acute phase and recovery, whereas hyperaemic CFV increased significantly after recovery (P<0.01) leading to a greater CFR (2.9+/-0.3 vs. 2.1+/-0.4, P<0.0001). At the acute phase, hyperaemic CFV was significantly correlated to WMS, ESV/m(2), but not to E/Ea, whereas at recovery, hyperaemic CFV was not correlated to LV parameters. The improvement of CFR was closely correlated to the decrease of ESV/m(2), of WMS, but not to diastolic parameters. No significant correlation was found between CFR and E/Ea or LV mass index at each stage. CONCLUSION: There is a transient impairment of CFR at the acute phase of TTC, which is due to a reduced vasodilating capacity. This impairment is closely correlated to LV systolic parameters. Diastolic compressive forces to the coronary microcirculation do not appear to play a critical role.

Prognostic value of transthoracic coronary flow reserve in medically treated patients with proximal left anterior descending artery stenosis of intermediate severity.

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.

Usefulness of two-dimensional longitudinal strain pattern to predict left ventricular recovery and in-hospital complications after acute anterior myocardial infarction treated successfully by primary angioplasty.

BACKGROUND: The aim of this study was to test the usefulness of two-dimensional longitudinal strain pattern in segments with wall motion abnormalities to predict left ventricular recovery and in-hospital cardiac events as well as coronary microvascular impairment (CMI) in patients with recent acute anterior myocardial infarction. METHODS: Forty-nine consecutive patients with acute myocardial infarction (mean age, 59 ± 13 years) treated successfully with primary coronary angioplasty prospectively underwent transthoracic Doppler echocardiography 24 hours after angioplasty and during follow-up (6 months). A two-dimensional strain analysis, including measurement of the duration of systolic lengthening expressed as a percentage of systolic duration (SL % duration), the lengthening-to-shortening ratio, the postsystolic shortening index in segments with wall motion abnormalities, and global longitudinal strain and left anterior descending coronary artery territory strain, was performed. Cardiac events were defined as a composite of death, reinfarction, and heart failure. CMI was assessed noninvasively by transthoracic Doppler left anterior descending coronary artery investigation <24 h after angioplasty and was defined as coronary flow velocity reserve < 1.7 and/or a no-reflow pattern (mean coronary flow velocity reserve, 1.8 ± 0.6 in the whole group). RESULTS: At the segmental level, SL % duration, lengthening-to-shortening ratio, and postsystolic shortening index were correlated with recovery (defined as normalization of wall motion abnormalities), whereas in multivariate analysis, only SL % duration independently predicted recovery (threshold level, 40%; area under the curve, 0.76; P < .01). At the patient level, in univariate analysis, SL % duration, global longitudinal strain, left anterior descending coronary artery territory strain, and troponin peak were correlated with recovery (defined as an absolute improvement of left ventricular ejection fraction of >5%). In multivariate analysis, SL % duration was independently related to recovery (area under the curve, 0.78; P < .01). Furthermore, SL % duration was independently linked to cardiac events (n = 13) and CMI (n = 24) (P < .01 for all). CONCLUSIONS: In patients with AMI treated by primary angioplasty, two-dimensional strain predicts left ventricular recovery independently of more traditional parameters and is independently linked to cardiac events and CMI.

Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

AIMS: The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. METHODS AND RESULTS: This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). CONCLUSIONS: FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves.

Relationship between acute strain pattern and recovery in tako-tsubo cardiomyopathy and acute anterior myocardial infarction: a comparative study using two-dimensional longitudinal strain.

After acute-anterior myocardial infarction (AMI), left ventricular (LV) viable myocardial segments show some degree of active deformation (longitudinal shortening) despite wall motion abnormalities (WMA). Tako-tsubo cardiomyopathy (TTC) is characterized by myocardial stunning; however, it is unclear whether in TTC the strain pattern mimics AMI. To compare the strain-pattern in TTC and AMI using the 2D-longitudinal strain by speckle-tracking in segments with WMA, and its relationship with recovery of function at follow-up. 21 consecutive patients with typical TTC and 21 age-matched AMI patients treated by primary angioplasty had an analysis of LV-longitudinal strain at the acute-phase and at follow-up (1 and 6 months later for TTC and AMI respectively). The recovery of a segment was defined as normal wall motion at follow-up. Among the 706 analyzable LV-segments at the acute-phase, 406 had WMA (TTC 229, AMI 177). At follow-up, total recovery was observed for 45 % segments in AMI and 100 % in TTC, (p < 0.01). At the acute phase, systolic lengthening duration (47 ± 43 vs. 18 ± 33 %) and amplitude (0.25 ± 0.29 vs. 0.09 ± 0.19) and post systolic shortening (67 ± 53 vs. 39 ± 38 %) were higher in TTC, when compared to AMI-recovery (all, p < 0.01). In AMI, systolic lengthening duration was an independent predictor of poor recovery in multivariate analysis, linked to segmental longitudinal strain at follow-up (all, p ≤ 0.01). Furthermore, among the 57 % of segments exhibiting any systolic lengthening duration in AMI, only » recovered, versus 62 % of such segments in TTC with 100 % recovery (p < 0.001). The systolic passive motion which is closely and inversely linked to recovery in AMI is paradoxically frequent and severe in TTC. This suggests that myocardial stunning in TTC and AMI is different according to longitudinal strain.

Impact of selective serotonin reuptake inhibitor therapy on heart valves in patients exposed to benfluorex: a multicentre study.

BACKGROUND: Given the association between valvular heart disease and drugs that alter serotonin metabolism, concerns have been raised about the possibility of an association between selective serotonin reuptake inhibitor (SSRI) use and drug-induced valvular disease. In France, SSRI use has been suggested to be an important confounding factor in the development of heart valve lesions in patients exposed to benfluorex in the context of the 'Médiator scandal'. AIMS: To address the relationship between SSRI use and valve regurgitation and morphology in a large cohort of patients exposed to benfluorex. METHODS: Overall, 832 consecutive patients exposed to benfluorex prospectively referred to 10 centres underwent complete echocardiography examinations according to a standardized protocol. Echocardiograms were independently and blindly read off-line by two experts. RESULTS: Ninety patients had been exposed to SSRIs for 3 months or more. The proportions of patients with no or trivial, mild, moderate or severe mitral regurgitation (MR) or aortic regurgitation (AR) were not different between SSRI patients and non-SSRI patients (P=0.63 and 0.58, respectively). The frequencies of AR ≥ mild (20 [22.2%] vs 145 [19.5%]; P=0.55) and MR ≥ mild (14 [15.6%] vs 118 [15.9%]; P=0.93) were similar in SSRI patients and non-SSRI patients. The frequencies of aortic and mitral valve abnormalities suggestive of drug-induced toxicity were also similar in the two patient groups. Multivariable logistic regression analysis confirmed the absence of any identifiable relationship between AR or MR and morphological abnormalities and SSRI use in the present cohort. CONCLUSION: Exposure to SSRIs was not associated with an increased risk of heart valve regurgitation or morphological abnormalities suggestive of drug-induced toxicity in this large cohort of patients exposed to benfluorex.

Factors associated with noninvasive coronary flow reserve in severe aortic stenosis.

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.

Comparison between non-invasive coronary flow reserve and fractional flow reserve to assess the functional significance of left anterior descending artery stenosis of intermediate severity.

BACKGROUND: Assessment of the functional significance of left anterior descending coronary artery (LAD) stenosis of intermediate severity (50%-70% diameter stenosis) is challenging. The aim of this study was to compare the value of noninvasive coronary flow reserve (CFR) with that of invasive fractional flow reserve (FFR) in the setting of LAD stenosis of angiographic intermediate severity. METHODS: Fifty stable consecutive patients (mean age, 63 ± 13 years; 11 women; mean left ventricular ejection fraction, 61 ± 10%) with angiographic proximal LAD stenoses of intermediate severity (55.5 ± 5% diameter stenosis on quantitative coronary angiography), no previous anterior myocardial infarction, and various vascular risk factors were prospectively studied. They underwent FFR assessment with intracoronary bolus adenosine (150 µg), and CFR assessment using intravenous adenosine (140 µg/kg/min over 2 min) in the distal part of the LAD on the same day in nearly all patients. CFR was defined as hyperemic peak diastolic LAD flow velocity divided by baseline flow velocity (normal value >2), and FFR was defined as distal pressure divided by mean aortic pressure during maximal hyperemia (normal value >0.8). RESULTS: The mean FFR and CFR were 0.84 ± 0.07 and 2.7 ± 0.75, respectively, in the whole population. Concordant results between FFR and CFR were seen in 44 patients (88%) and discordant results in six patients (12%). There was a significant correlation between CFR and FFR (r = 0.59, P < .01). A better correlation was found between FFR and percentage LAD diameter stenosis, and lesion length (all P values < .05), than between CFR and the same anatomic markers of stenosis severity (all P values = NS). The sensitivity, specificity, and positive and negative predictive values of CFR >2 to detect a nonsignificant lesion defined by normal FFR were 95%, 69%, 90%, and 82%, respectively. CONCLUSIONS: In patients with LAD stenosis of intermediate severity, discordant results between noninvasive CFR and FFR were not unusual, and the anatomic determinants of the stenosis were better correlated to FFR than to CFR. However, CFR, which is a global evaluation of the coronary tree, has very high sensitivity to detect a nonsignificant lesion, despite the high prevalence of vascular risk factors.

Non-invasive coronary flow reserve after successful primary angioplasty for acute anterior myocardial infarction is an independent predictor of left ventricular recovery and in-hospital cardiac events.

BACKGROUND: The prediction of left ventricular (LV) recovery and adverse cardiac events after reperfused acute myocardial infarction (AMI) is challenging. The aim of this study was to assess the usefulness of noninvasive coronary flow reserve (CFR) to predict LV recovery and in-hospital adverse cardiac events after AMI by comparison with other available tools. METHODS: Fifty-five consecutive patients (mean age, 59 +/- 13 years; 33% women) with first reperfused ST-elevation anterior AMIs and sustained Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow underwent prospectively, < 24 hours after successful primary coronary angioplasty, standard echocardiography and noninvasive CFR assessment in the distal part of the left anterior descending coronary artery, using intravenous adenosine infusion, while in a stable hemodynamic situation. CFR was defined as peak hyperemic left anterior descending coronary artery flow velocity divided by baseline flow velocity. LV ejection fraction (LVEF) was measured using the biplane Simpson's rule. A no-reflow pattern was defined as diastolic deceleration time of basal diastolic coronary flow velocity < 600 ms and/or systolic flow reversal and recovery of LV function as an absolute increase of LVEF >or= 10% at 3-month follow-up. Adverse events were defined as the composite of death, recurrent AMI, and acute heart failure. RESULTS: In the whole population, the mean LVEF was 46 +/- 5% at baseline and 55 +/- 9% at follow-up. Patients without LV recovery had more severely impaired CFR compared with those with LV recovery (2.1 +/- 0.55 vs 1.46 +/- 0.2, P < .001), as did patients with adverse events compared with those without events (P = .01). Furthermore, CFR was significantly correlated with 3-month LVEF and regional wall motion score (both P values < .01). On multivariate analysis, CFR was an independent predictor of global and regional LV function at follow-up (both P values

Evaluation of left anterior descending coronary artery stenosis of intermediate severity using transthoracic coronary flow reserve and dobutamine stress echocardiography.

BACKGROUND: The physiologic significance of left anterior descending coronary artery (LAD) stenosis of intermediate angiographic severity is of clinical importance and difficult to assess. Assessment of coronary flow reserve (CFR) by Doppler transthoracic echocardiography (TTE) is a new tool and could allow rapid, noninvasive evaluation of stenosis severity in this setting. OBJECTIVE: We sought to evaluate the value of CFR measurement determined by TTE, compared with dobutamine stress echocardiography (DSE), in the setting of LAD stenosis of intermediate angiographic severity. METHODS: A total of 51 consecutive stable patients in sinus rhythm (33 men; age 65 +/- 12 years; left ventricular ejection fraction 59 +/- 7%) with no previous anterior myocardial infarction and with an angiographic proximal LAD stenosis of intermediate severity (56 +/- 8% quantitative coronary angioplasty) 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, using a multifrequency transducer, in the modified parasternal or 3-apical view. CFR was calculated as the ratio of hyperemic to basal mean (mean CFR) and peak (peak CFR) diastolic flow velocity. DSE was performed immediately after the adenosine test to assess ischemia in the LAD territory (percent maximum predicted heart rate = 94 +/- 8). RESULTS: Adequate recording of CFR was possible in 46 patients. Of the 35 patients with a CFR of 2 or more (peak CFR = 2.7 +/- 0.6), DSE was normal in 34. Of the 11 patients with a CFR less than 2 (peak CFR = 1.7 +/- 0.2), 7 had an abnormal response with DSE in the LAD territory. In this range of intermediate stenosis, there was a poor correlation between percent LAD diameter stenosis and CFR. For patients with positive DSE, CFR was 1.6 +/- 0.2 compared with 2.7 +/- 0.6 for patients with normal DSE (P < .05). The sensitivity, specificity, and the positive and negative predictive values of TTE CFR for detecting ischemia on DSE were 88%, 89%, 64%, and 97%, respectively, with an overall agreement of 89% between the two tests. CONCLUSION: Given its high negative predictive value, noninvasive CFR could be a useful aid in reaching clinical decisions promptly at the bedside in patients with moderately severe lesions of the proximal LAD.