Hyperemic Flow Velocity Research Articles

Microvascular Remodeling on Endomyocardial Biopsy and Coronary Flow Reserve by Transthoracic Doppler Echocardiography in Heart Transplant Patients: A Clinical-Pathological Study

Purpose Cardiac allograft vasculopathy (CAV) is the main limiting factor of long-term survival after heart transplantation (HT). CAV affects both epicardial coronary vessels and microvasculature. Coronary flow reserve (CFR) by transthoracic Doppler echocardiography (TDE) is an independent predictor of death in HT patients. The aim of the study was to correlate the microvascular remodeling, as assessed by endomyocardial biopsy (EMB), with CFR by TDE in HT patients with normal coronary angiograms. Methods and Materials We studied 28 consecutive HT patients without angiographic CAV (25 male, aged 54±10 years at HT, time from HT 7.5±5 years). Coronary flow velocity in the left anterior descending coronary artery was detected by TDE at rest and during adenosine infusion. CFR was the ratio of hyperaemic diastolic flow velocity (DFV) to resting DFV. A CFR≤2.5 was considered abnormal. In the 1 st year post-HT EMBs, myocytes diameter, fibrosis percentage, capillary density and microvascular remodeling (vessel media area/total vessel area ratio (%)) were evaluated by digital morphometry. Results Microvascular remodeling was higher in patients with CFR≤2.5 (39.2% 11/28 pts) compared with patients with CFR>2.5 (72.3±8 vs 65.2±4.7 %, p Conclusions Our results suggest that coronary microvascular remodeling at EMBs may be the main predictor of abnormal CFR in HT patients. CFR by TDE may be a useful noninvasive tool in the evaluation of microvascular dysfunction/damage in HT. Further studies are warranted.

Resting Coronary Haemodynamics are Stable and Reproducible When Retested After 6 Months in Patients with Non-obstructive Coronary Artery Disease

Background: Vasodilator-free indices of coronary stenosis severity require stability of resting coronary hemodynamics. It is unknown whether resting hemodynamics are sufficiently reproducible to be reliable over an extended period. We evaluate the long-term stability of resting and hyperemic intracoronary pressure and flow velocity measurements over a 6-month period. Methods: 17 patients (mean age 55+/-12), with 18 anatomically mild-to-moderate lesions (17 in the mid-left anterior descending artery and 1 circumflex artery) had invasive simultaneous pressure and flow velocity measurements made at rest and during intravenous adenosine infusion (140mcg/kg/min). Measurements were repeated after 6 months at the same vessel location. Changes in coronary flow velocity and microcirculatory resistance were compared using Students T-test and the F-test. Results: Mean flow velocity at rest was similar at baseline and 6 months (22.2+/-8.5cm/s vs 21.6+/-8.5cm/s, p1⁄40.78); hyperemic mean flow (43.3+/-14.1cm/s vs 46.5+/-11.5cm/s, p1⁄40.47) similarly did not significantly change. The mean change between baseline and 6 months was 4% and 17% for resting and hyperemic flow respectively and this was not significantly different (p1⁄40.27). Peak coronary flow velocity was also similar at both time points at rest (53.5+/-27.2cm/s vs 46.9+/-20.3cm/s, p1⁄40.38) and hyperemia (88.0+/-22.5cm/s vs 90.4+/-24.6cm/s, p1⁄40.75); the mean change was 3.0% and 9.0% respectively (p1⁄40.50). Microcirculatory resistance measured at rest was unchanged between baseline and 6 months at rest (4.97+/-2.37mmHg/cm.s vs 5.23+/-2.25mmHg/cm.s, p1⁄40.58) and during hyperemia (1.94+/-0.72 vs

Flow-Mediated Dilation Normalization Predicts Outcome in Chronic Heart Failure Patients

BackgroundReduced flow-mediated dilation (FMD) is a known prognostic marker in heart failure (HF), but may be influenced by the brachial artery (BA) diameter. Aiming to adjust for this influence, we normalized FMD (nFMD) by the peak shear rate (PSR) and tested its prognostic power in HF patients. Methods and ResultsBA diameter, FMD, difference in hyperemic versus rest brachial flow velocity (FVD), PSR (FVD/BA), and nFMD (FMD/PSR × 1000) were assessed in 71 HF patients. At follow-up (mean 512 days), 19 HF (27%) reached the combined endpoint (4 heart transplantations [HTs], 1 left ventricle assist device implantation [LVAD], and 14 cardiac deaths [CDs]). With multivariate Cox regression analysis, New York Heart Association functional class ≥III (hazard ratio [HR] 9.36, 95% confidence interval [CI] 2.11–41.4; P = .003), digoxin use (HR 6.36, 95% CI 2.18–18.6; P = .0010), FMD (HR 0.703, 95% CI 0.547–0.904; P = .006), PSR (HR 1.01, 95% CI 1.005–1.022; P = .001), FVD (HR 1.04, 95% CI 1.00–1.06; P = .02), and nFMD (HR 0.535, 95% CI 0.39–0.74; P = .0001) were predictors of unfavorable outcome. Receiver operating characteristic curve for nFMD showed that patients with nFMD >5 seconds had significantly better event-free survival than patients with nFMD ≤5 seconds (log-rank test: P < .0001). ConclusionsnFMD is a strong independent predictor of CD, HT, and LVAD in HF with left ventricular ejection fraction <40%. Patients with nFMD >5 seconds have a better prognosis than those with lower values.

La réserve coronaire non invasive est un prédicteur indépendant de la capacité d’exercice après infarctus antérieur aigu

BackgroundAfter acute myocardial infarction (MI) coronary microvascular impairment and reduced exercise capacity are both determinant of prognosis. ObjectiveWe tested whether non-invasive coronary flow reserve (CFR) performed after MI predicts post-MI exercise capacity (EC). MethodsFifty 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. ResultsThe 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). ConclusionContrarily 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.

Factors Associated with Noninvasive Coronary Flow Reserve in Severe Aortic Stenosis

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%). 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. 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). 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.

Analysis of coronary flow haemodynamics in homozygous familial hypercholesterolaemic adolescents with aortic supravalvular stenosis

To study coronary artery haemodynamics in adolescents with homozygous familial hypercholesterolaemia and aortic supravalvular stenosis. Patients diagnosed with familial hypercholesterolaemia who were younger than 16 years and who had undergone transthoracic echocardiography from 2007 to 2010 were included in this study. We included patients with homozygous familial hypercholesterolaemia and aortic supravalvular stenosis and those with heterozygous familial hypercholesterolaemia. All patients underwent stress echocardiography, and left anterior descending coronary artery flow was successfully detected. Coronary flow velocity reserve was calculated as the ratio of hyperaemic mean diastolic flow velocity after injection of adenosine to basal mean diastolic flow velocity. Changes in coronary haemodynamics and the relationship between lipid concentrations were determined. A total of 11 patients with homozygous familial hypercholesterolaemia were enrolled in this study. Lipid concentrations were measured, and the mean coronary flow velocity reserve was 1.97 plus or minus 0.51. Seven children were included in the group of patients with heterozygous familial hypercholesterolaemia. In these children, the mean coronary flow velocity reserve was 3.08 plus or minus 0.84. The coronary flow velocity reserve of homozygous familial hypercholesterolaemic patients is lower than that of heterozygous familial hypercholesterolaemic patients, and it is associated with a high concentration of low-density lipoprotein cholesterol. Aortic stenosis and plaques compromised the ostia of the coronary artery and caused increased basal mean diastolic coronary velocity with blunted increase in peak velocity, which decreased the coronary flow velocity reserve.

Brachial artery hyperaemic blood flow velocity in relation to established indices of vascular function and global atherosclerosis

Systolic to diastolic blood flow velocity (SDFV) ratio in the brachial artery recently proved to be related to cardiovascular risk and carotid atherosclerosis. We hypothesized that the SDFV ratio was related to established markers of vascular function and global atherosclerosis. Established markers of endothelial function in forearm resistance vessels, flow-mediated vasodilation and arterial stiffness were assessed in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study including 1016 individuals aged 70. Whole-body magnetic resonance angiography was performed in a random 306 of the participants. Atherosclerotic lesions were summarized in a total atherosclerotic score (TAS). Before and during hyperaemia of the brachial artery, systolic and diastolic blood flow velocities were measured by Doppler. The SDFV ratio was positively related to endothelium-independent vasodilatation, while inverse relations were found to flow-mediated dilation, common carotid artery distensibility and the stroke volume to pulse pressure ratio. Endothelium-dependent vasodilatation and total peripheral resistance index were not significantly related to the SDFV ratio. The SDFV ratio (P = 0·015) and the blood flow increase (BFI) during hyperaemia (P = 0·020) were both significantly related to TAS after gender adjustment. When adjusted for the Framingham risk score, both the SDFV ratio (P = 0·057) and BFI (P = 0·078) lost somewhat in significance. The SDFV ratio was related to established markers of both vasodilation and arterial compliance, and to global atherosclerosis. Future larger studies have to evaluate whether the SDFV ratio is related to global atherosclerosis independently of traditional risk factors.

Impaired coronary flow reserve in young patients affected by severe psoriasis

ObjectiveOur study aimed to evaluate the effects of psoriasis (Pso) on coronary microvascular function and whether there is a relationship between disease activity scores and coronary blood flow abnormalities. Methods56 young patients (pts) with Pso (42 M, aged 37±3 years) without clinical evidence of cardiovascular diseases, and 56 controls matched for age and gender were studied. Coronary flow velocity in the left anterior descending coronary artery was detected by transthoracic echocardiography at rest and during adenosine infusion. Coronary flow reserve (CFR) was the ratio of hyperaemic diastolic flow velocity (DFV) to resting DFV. A CFR≤2.5 was considered abnormal. ResultsIn pts with Pso, CFR was lower than in controls (3.2±0.9 vs. 3.7±0.7, p=0.02). CFR was abnormal (≤2.5) in 12 pts (22% vs. 0% controls, p<0.0001). Moreover, in pts with CFR≤2.5, Psoriasis Area Severity Index (PASI), a clinical score for Pso severity, was higher (11±6 vs. 7±3, p=0.006) compared to pts with CFR>2.5. At multivariable analysis PASI remained the only determinant of CFR≤2.5 (p=0.02). ConclusionCFR in young pts with severe Pso without coronary disease is reduced suggesting a coronary microvascular dysfunction, independently related to the severity and extension of Pso. This early microvascular impairment might be hypothesized as the consequence of prolonged and sustained systemic inflammation and might explain the increased cardiovascular risk conferred by Pso.

New method to measure coronary velocity and coronary flow reserve

Coronary flow reserve (CFR) is an important index of coronary microcirculatory function. The objective of this study was to validate the reproducibility and accuracy of intravascular conductance catheter-based method for measurements of baseline and hyperemic coronary flow velocity (and hence CFR). The absolute coronary blood velocity was determined by measuring the time of transit of a saline injection between two pairs of electrodes (known distance) on a conductance catheter during a routine saline injection without the need for reference flow. In vitro validation was made in the velocity range of 5 to 70 cm/s in reference to the volume collection method. In 10 swine, velocity measurements were compared with those from a flow probe in coronary arteries at different CFR attained by microsphere embolization. In vitro, the mean difference between the proposed method and volume collection was 0.7 ± 1.34 cm/s for steady flow and -0.77 ± 2.22 cm/s for pulsatile flow. The mean difference between duplicate measurements was 0 ± 1.4 cm/s. In in vivo experiments, the flow (product of velocity and lumen cross-sectional area that is also measured by the conductance catheter) was determined in both normal and stenotic vessels and the mean difference between the proposed method and flow probe was -1 ± 12 ml/min (flow ranged from 10 to 130 ml/min). For CFR, the mean difference between the two methods was 0.06 ± 0.28 (range of 1 to 3). Our results demonstrate the reproducibility and accuracy of velocity and CFR measurements with a conductance catheter by use of a standard saline injection. The ability of the combined measurement of coronary lumen area (as previously validated) and current velocity and CFR measurements provides an integrative diagnostic tool for interventional cardiology.

Brachial artery hyperaemic blood flow velocity and left ventricular geometry

Cardiovascular risk factors and carotid atherosclerosis relate to blood flow velocity in the brachial artery during induced hyperaemia. This relation proved to be particularly strong when using the hyperaemic systolic to diastolic blood flow velocity (SDFV) ratio. In this study, we further investigated this ratio in relation to the left ventricular (LV) geometry in a cross-sectional analysis. In the Prospective Investigation of the Vasculature in Uppsala Seniors study, 1016 seventy-year-olds participated. Blood flow velocity during hyperaemia of the brachial artery by Doppler was analysed. Echocardiography was performed, allowing analysis of LV geometry, categorised into four different groups: normal, concentric remodelling, concentric and eccentric hypertrophy. The SDFV ratio increased in subjects with concentric LV-remodelling (P=0.006) or LV-hypertrophy (P=0.001), but not in those with eccentric hypertrophy (P=0.12) when compared with the group with normal LV geometry. These associations remained significant after adjustment for gender, blood pressure, blood glucose, body mass index and antihypertensive treatment. The SDFV ratio in the brachial artery was related to concentric geometry of the LV in an elderly population sample, suggesting this new hemodynamic variable as a marker of increased afterload. Future studies have to determine if the SDFV ratio is a powerful predictor of future CV events, in addition to LV geometry.

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

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. 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). 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. 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.

128 Comparison between non invasive coronary flow reserve and fractional flow reserve in the setting of left anterior descending artery stenosis of intermediate severity

The functional significance of left anterior descending artery (LAD) stenosis of angiographic intermediate severity (IS) (50–70% diameter stenosis) is challenging. to compare the value of non-invasive coronary flow reserve (CFR) to the invasive fractional flow reserve (FFR) in patients (pts) with LAD stenosis of IS. 46 consecutive pts (mean age 63 ± 13 years, 11 females, mean LVEF 63 ± 8%) with various risk factors (diabetes 17%, hypertension 52%, smoking 28%, dyslipidemia 74%), no previous anterior myocardial infarction, and with an LAD stenosis of IS (55 ± 5% diameter stenosis, QCA) were prospectively studied. They underwent FFR with intracoronary bolus adenosine (150 μg), 3 cms distal to the stenosis, and CFR using intravenous adenosine (140 μg/kg/min over 2 min), in the distal part of the LAD, the same day in nearly all cases. 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). The mean FFR and CFR were 0.84 ± 0.07 and 2.8 ± 0.7 respectively. Concordant results between FFR and CFR were seen in 39 cases (85%) and discordant results in 7 cases (15%). There was a weak correlation between CFR and FFR (r = 0.43, p < 0.01). A better correlation was found between FFR and LAD diameter stenosis (r = −0.42, p < 0.01) than between CFR and LAD diameter stenosis (r = −0.23, p = 0.1), and between FFR and lesion length (r = −0.39, p < 0.05) than between CFR and lesion length (r = −0.27, p = 0.1). However, the sensitivity and the positive predictive value of CFR ≥2 to detect a non significant lesion defined by a normal FFR were high (94.5% and 87.5% respectively) in this setting. In pts with LAD stenosis of IS, discordant results between CFR and FFR were not unusual, and the anatomic determinants of the stenosis are better correlated to FFR than to CFR. However, CFR which is a global evaluation of the coronary tree has a very high sensitivity to detect a non significant lesion, despite the high prevalence of vascular risk factors.

Ivabradine improves coronary flow reserve in patients with stable coronary artery disease

ObjectivesAlthough treatment with ivabradine reduces the incidence of hospital admissions for myocardial infarction and coronary revascularisation, there are no data concerning its effect on coronary circulation. The purpose of this study was to assess the effects of ivabradine on coronary flow velocity and flow reserve (CFR) in patients with stable coronary artery disease (CAD). MethodsDuring diagnostic coronary angiography (baseline), twenty-one patients with stable CAD underwent coronary flow velocity measurements (APVcm/s) in a non-culprit vessel, using a Doppler guidewire, at rest (r) and after adenosine administration to achieve maximal hyperaemia (h). During programmed coronary intervention in the culprit vessel, the same measurements were repeated one week after treatment with ivabradine (5mg twice daily), both at the intrinsic heart rate and at a paced heart rate identical to that before treatment. CFR was defined as h-APV/r-APV. ResultsHeart rate was significantly lower after treatment with ivabradine (78±14bpm vs 65±9bpm, p<0.001). Also, a reduction of r-APV (17.0±5.5 vs 19.7±7.6, p=0.003) and augmentation of h-APV (57.9±17.8 vs 53.5±21.4, p=0.009) leading to CFR improvement (3.51±0.81 vs 2.78±0.61, p<0.001) were observed. During pacing, although r-APV reverted to values similar to those before treatment (20.0±6.5 vs 19.7±7.6, p=NS), a sustained improvement in h-APV was observed (59.5±19.7 vs 53.5±21.4, p=0.007) and CFR remained higher than before treatment (3.04±0.66 vs 2.78±0.61, p<0.001). ConclusionsIvabradine treatment significantly improves hyperaemic coronary flow velocity and CFR in patients with stable CAD. These effects remain even after heart rate correction indicating improved microvascular function.

Evaluation of Coronary Flow Velocity Reserve in Homozygous Familial Hypercholesterolemia by Transthoracic Doppler Echocardiography and Dual-Source Computed Tomography

Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis and usually occurs at the ostia of coronary arteries. In this study, we used transthoracic Doppler echocardiography (TTDE) to evaluate the dynamic changes of coronary flow in HoFH patients and to detect aortic and coronary atherosclerosis by dual-source computed tomography (DSCT). We studied 20 HoFH patients (12 females, 8 males, mean age 13.1 ± 5.3 years, with a mean low density lipoprotein (LDL) cholesterol of 583 ± 113 mg/dL) and 15 control patients (8 females, 7 males, mean age 15.2 ± 6.9 years, with a mean LDL cholesterol 128 ± 71 mg/dL) using TTDE and DSCT. None of the patients showed evidence of ischemia with standard exercise testing. Though the baseline coronary flow was similar between HoFH patients and normal controls, the hyperemic flow velocities and, thus, the coronary flow velocity reserve (CFVR) were significantly lower in those with HoFH. All HoFH patients had aortic plaques, nine of them with the coronary artery ostia simultaneously, who had significantly higher LDL-cholesterol and lower CFVR than those without ostia plaques. Our data demonstrated that TTDE together with DSCT could be a useful noninvasive method for detection of coronary flow dynamics and atherosclerosis specifically in HoFH subjects with coronary ostia. (E-mail: lizhian_anzhen@yahoo.com.cn)

Noninvasive Evaluation of Coronary Flow Velocity Reserve in Homozygous Familial Hypercholesterolemia by Transthoracic Doppler Echocardiography

To evaluate the value of transthoracic Doppler echocardiography (TTDE) of the left anterior descending coronary for the detection of early abnormalities of coronary arteries in asymptomatic patients with homozygous familial hypercholesterolemia (HoFH). Seventeen asymptomatic patients with HoFH and 10 controls had plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides measured and underwent TTDE of their left coronary descending artery to determine peak and mean flow velocities under basal conditions and under hyperemia induced by adenosine infusion. Coronary flow velocity reserve (CFVR) was calculated from the mean flow velocities. The presence of aortic supravalvular stenosis was also determined from supravalvular flow velocity and aortic valve thickening values. HoFH patients had similar basal but significantly lower hyperemic flow velocities and CFVR than control patients. Eight of the 17 HoFH patients had supravalvular aortic stenosis, and these patients had significantly higher LDL cholesterol and lower CFVR than those without this stenosis. Treatment with lipid-lowering drugs lowered lipid levels and increased CFVR values, but neither of these parameters reached normal values. TTDE is a suitable noninvasive technique to detect early abnormalities of coronary arteries and to monitor the clinical efficacy of lipid-lowering treatment in asymptomatic HoFH patients.

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

To assess the usefulness of non-invasive coronary flow reserve (CFR) to predict left ventricular adverse remodelling (LVR) after ST-elevation myocardial infarction (STEMI). 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). Non-invasive CFR is an independent predictor of LVR after successful primary angioplasty of anterior STEMI.

Visceral and Subcutaneous Adiposity and Brachial Artery Vasodilator Function

Endothelial dysfunction may link obesity to cardiovascular disease (CVD). We tested the hypothesis that visceral abdominal tissue (VAT) as compared with subcutaneous adipose tissue (SAT) is more related to endothelium-dependent vasodilation. Among Framingham Offspring and Third Generation cohorts (n = 3,020, mean age 50 years, 47% women), we used multivariable linear regression adjusted for CVD and its risk factors to relate computed tomography (CT)-assessed VAT and SAT, BMI, and waist circumference (WC), with brachial artery measures. In multivariable-adjusted models, BMI, WC, VAT, and SAT were positively related to baseline artery diameter and baseline mean flow velocity (all P < 0.001), but not hyperemic mean flow velocity. In multivariable-adjusted models, BMI (P = 0.002), WC (P = 0.001), and VAT (P = 0.01), but not SAT (P = 0.24) were inversely associated with percentage of flow-mediated dilation (FMD%). However, there was little incremental increase in the proportion of variability explained by VAT (R(2) = 0.266) as compared to SAT (R(2) = 0.265), above and beyond traditional risk factors. VAT, but not SAT was associated with FMD% after adjusting for clinical covariates. Nevertheless, the differential association with VAT as compared to SAT was minimal.

Brachial artery diameter, blood flow and flow-mediated dilation in sleep-disordered breathing

Clinic-based, case-control studies linked sleep-disordered breathing (SDB) to markers of endothelial dysfunction. We attempted to validate this association in a large community-based sample, and evaluate the relation of SDB to arterial diameter and peripheral blood flow. This community-based, cross-sectional observational study included 327 men and 355 women, aged 42-83 years, from the Framingham Heart Study site of the Sleep Heart Health Study. The polysomnographically derived apnea-hypopnea index and the hypoxemia index (percent sleep time with oxyhemoglobin saturation below 90%) were used to quantify the severity of SDB. Brachial artery ultrasound measurements included baseline diameter, percent flow-mediated dilation, and baseline and hyperemic flow velocity and volume. The baseline brachial artery diameter was significantly associated with both the apnea-hypopnea index and the hypoxemia index. The association was diminished by adjustment for body mass index, but remained significant for the apnea-hypopnea index. Age-, sex-, race- and body mass index-adjusted mean diameters were 4.32, 4.33, 4.33, 4.56, 4.53 mm for those with apnea-hypopnea index < 1.5, 1.5-4.9, 5-14.9, 15-29.9, >/= 30, respectively; p = 0.03. Baseline flow measures were associated with the apnea-hypopnea index but this association was non-significant after adjusting for body mass index. No significant association was observed between measures of SDB and percent flow-mediated dilation or hyperemic flow in any model. In conclusion, this study supports a moderate association of SDB and larger baseline brachial artery diameter, which may reflect SDB-induced vascular remodeling. This study does not support a link between SDB and endothelial dysfunction as measured by brachial artery flow-mediated dilation.

Nebivolol induces parallel improvement of left ventricular filling pressure and coronary flow reserve in uncomplicated arterial hypertension

Our aim was to analyze the effects of 3-month antihypertensive therapy by nebivolol, a beta-blocking agent with nitric oxide-mediated vasodilatory properties, on coronary flow reserve (CFR) and left ventricular filling pressure (LVFP) in uncomplicated arterial hypertension. Twenty newly diagnosed, never treated, uncomplicated hypertensive patients (14 male and six female patients, mean age = 49 years), I-II WHO grade, underwent single-blind nebivolol treatment. At baseline and at 3-month follow-up, patients underwent Doppler echocardiography including pulsed Tissue Doppler of septal mitral annulus: the ratio between transmitral E velocity and myocardial early diastolic velocity (E/Em ratio) was calculated as an index of LVFP degree. Transthoracic Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was also determined. After 3-month nebivolol therapy, rate-pressure product decreased (P < 0.0001). No significant change of left ventricular mass index, relative wall thickness and midwall shortening was detected. Left ventricular end-diastolic diameter and stroke volume were both marginally increased. Nebivolol increased Em (P < 0.0001), reduced E/Em ratio (from 9.0 +/- 1.6 to 8.2 +/- 1.1, P < 0.0001) and enhanced CFR (from 2.07 +/- 0.2 to 2.20 +/- 0.2, P = 0.003), because of increased hyperemic coronary flow velocity (P < 0.001). CFR increase remained significant (P < 0.001) after normalizing resting and dipyridamole coronary velocities for the respective rate-pressure product. The increase of normalized CFR induced by nebivolol was related with E/Em ratio decrease (r = -0.65, P < 0.002). Nebivolol improves LVFP as well as CFR in uncomplicated hypertension. The association between changes of CFR and those of LVFP indicates a possible common denominator between improvement of coronary microvascular function and myocardial stimulation of nitric oxide release induced by the drug.

Brachial artery hyperemic blood flow velocities are related to carotid atherosclerosis

Cardiovascular (CV) risk relates to the blood flow velocity pattern in the brachial artery during hyperemia, especially to the hyperaemic systolic to diastolic mean blood flow velocity (SDFV) ratio. Here, we investigated the relations between SDFV in the brachial artery and different characteristics of carotid atherosclerosis. Data were collected from 1016 70-year-olds participating in the Prospective Investigation of Uppsala Seniors study. Doppler recordings of blood flow velocity during hyperemia were analysed in the brachial artery. In the carotid artery, intima-media thickness (IMT) was recorded together with an assessment of echogenicity by the Grey scale median (GSM) method in both overt plaques and in the intima-media complex (IM-GSM). The SDFV ratio was related to the number of carotid arteries affected by plaque (P = 0.018) and inversely to plaque echogenicity (P = 0.0003). The SDFV ratio was also related to IMT (P = 0.0022) and inversely to IM-GSM (P = 0.0001). These relations were statistically significant also after adjusting for major CV risk factors, individually as well as summarised as the Framingham risk score. Our results indicate that the hyperemic systolic to diastolic blood flow velocity ratio in the brachial artery is related to atherosclerosis in the carotid artery.