Hyperemic Flow Velocity Research Articles

Coronary Flow Velocity Reserve in Patients with Ascending Aorta Aneurysm

Ascending aorta aneurysms (AAA) are one of the leading causes of morbidity and mortality. Impairment in coronary flow may contribute to cardiovascular consequences in AAA patients. Coronary flow velocity reserve (CFVR) has been considered an important diagnostic index of the functional capacity of coronary arteries noninvasively. The aim of this study was to evaluate, by noninvasive CVFR, whether patients with AAA demonstrate significant coronary microvascular dysfunction in the absence of coronary artery disease (CAD). We prospectively included 44 patients with thoracic AAA in the absence of concomitant CAD (30 men, 14 women; mean age 57.5±8.4years). A total of 36 patients without aortic dilatation (mean age 55.2±9.9years) were selected as the control group. Coronary flow velocities in the distal left anterior descending (LAD) artery were measured using transthoracic echocardiography. CFVR was calculated as the hyperemic to resting coronary diastolic peak velocities ratio. Compared with controls, patients with AAA had higher baseline LAD peak diastolic coronary flow velocities (28.3±5.8 vs. 25.2±4.5cm/sec, P=0.01), lower hyperemic LAD flow velocities (54.0±10.3 vs. 57.2±12.7cm/sec, P=0.220), and consequently lower CFVR (1.9±0.3 vs. 2.3±0.5, P<0.001). Multivariate linear regression analysis showed that CFVR was independently associated only with aortic systolic diameter (AoSD) (β=-0.679, P=<0.001). Our study demonstrates that noninvasive CFVR is significantly reduced in patients with AAA and AoSD is the most important determinant of impaired CFVR.

Association of Peripheral Microvascular Dysfunction and Erectile Dysfunction

Increasing evidence of a link between erectile dysfunction and cardiovascular disease suggests a shared vascular etiology with endothelial dysfunction as a plausible underlying biological mechanism. To our knowledge whether this association is different for large arterial endothelium compared to microvascular endothelium has not yet been established. We investigated the association of erectile dysfunction with macrovascular and microvascular endothelial function. A sample of 390 men with a mean age of 55.5 years was recruited from the BACH survey, a population based survey of urological symptoms. Erectile dysfunction was assessed using IIEF-5. The percent of brachial artery flow mediated dilatation, a measure of macrovascular function, and hyperemic flow velocity in cm per second, a measure of microvascular function, were assessed by ultrasound. Linear regression was used to assess the association of erectile dysfunction and endothelial function, and adjust for potential confounders. Reactive hyperemia was lower in men with vs without erectile dysfunction (mean ± SE 97.1 ± 2.5 vs 106.0 ± 1.6 cm per second, p = 0.003). However, the difference in flow mediated dilatation between men with vs without erectile dysfunction was statistically nonsignificant (mean 6.6% ± 0.33% vs 7.2% ± 0.24%, p = 0.147). The association of erectile dysfunction with reactive hyperemia was attenuated but it remained statistically significant in men with moderate to severe erectile dysfunction (IIEF-5 less than 12) after adjusting for traditional cardiovascular risk factors (p = 0.038). These results provide evidence of greater microvascular than macrovascular endothelial dysfunction as a potential contributor to erectile dysfunction and an underlying mechanism linking erectile dysfunction and cardiovascular disease.

Everolimus Prevents Coronary Microvasculopathy in Heart Transplant Recipients With Normal Coronary Angiograms: An Anatomo-Functional Study

BackgroundCoronary allograft vasculopathy (CAV) involves both epicardial vessels and coronary microcirculation. Little is known about the effect of everolimus on coronary microvasculopathy in heart transplantation (HT). The aim of our study was to assess the pathological substrate of coronary flow reserve (CFR) impairment in HT patients and the effect of everolimus on microvascular remodeling and CFR. MethodsWe studied 28 HT patients with normal coronary angiograms (25 male, age at HT 54 ± 10 years). Immunosuppressive regimen consisted of cyclosporine and everolimus (10 patients) or mycophenolate mophetil (18 patients). They were evaluated with digital microscopy for morphometric analysis of fibrosis and microvascular remodeling. Coronary flow velocity in the left anterior descending coronary artery was detected using transthoracic Doppler echocardiography 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 and sign of coronary microvascular dysfunction. ResultsIn patients with CFR ≤2.5 the thickness of the tunica media of intramyocardial arterioles was greater than in patients with CFR >2.5 (39 ± 2 vs 17 ± 3 μm; P = .02). Microvascular remodeling was significantly higher in patients with CFR ≤2.5 (72.7 ± 2.4 vs 50.4 ± 8.4%; P < .007). Capillary density and fibrosis were comparable between groups (157.2 ± 42.4 vs 175.7 ± 42.4 capillaries/mm2; P = .3; and 6.8 ± 5 vs 8.3 ± 4.9%; P = .4, respectively). The thickness of the tunica media of intramyocardial arterioles was lower in patients whose therapy included everolimus (15 ± 2 vs 32 ± 4 μm, P = .03) and CFR was higher (3.2 ± 0.5 vs 2.8 ± 0.9; P = .03). ConclusionThe pathological substrate of reduced CFR in HT patients seems to be a hypertrophic remodeling of coronary arterioles. Everolimus appears to prevent such microvascular remodeling and preserve coronary flow reserve.

Effects of ranolazine on noninvasive coronary flow reserve in patients with myocardial ischemia but without obstructive coronary artery disease.

Ranolazine reduces the Na-dependent calcium overload via inhibition of the late sodium current, improving diastolic tone and oxygen handling during myocardial ischemia. In patients with angina, evidence of myocardial ischemia, but no obstructive coronary artery disease (CAD), abnormal coronary autoregulation plays a key role. Transthoracic Doppler-derived coronary flow reserve (CFR) is an index of coronary arterial reactivity and decreases in both microvascular dysfunction and coronary artery stenosis. The aim of this study was to assess the effect of ranolazine on CFR in this group of patient. Fifty-eight (39M, 19F) patients with angina and evidence of myocardial ischemia, but no obstructive CAD, were enrolled in a double-blind, placebo-controlled trial. Participants were assigned to ranolazine (29) or placebo (29) for 8 weeks (up to 500 mg twice a day). CFR was determined as the ratio of hyperemic, induced by intravenous dypiridamole administration, to baseline diastolic coronary flow velocity. CFR was assessed before and after 8-week therapy. CFR was successfully performed in all patients. There were no significant differences in baseline characteristics and CFR between ranolazine and placebo group. After 8 weeks CFR significantly increased in ranolazine group (2.54 ± 0.44 vs. 1.91 ± 0.31; P = 0.005) but not in placebo group (1.99 ± 0.32 vs. 1.94 ± 0.29; P = ns). No patient dropped out during 8 weeks therapy. Side effects were similar in both groups. Ranolazine is able to improve CFR in these patients. This is probably due to improvement in abnormal coronary autoregulation, both reducing baseline diastolic coronary flow velocity and increasing hyperemic diastolic coronary flow velocity.

Relation of Long-Term Exposure to Air Pollution to Brachial Artery Flow-Mediated Dilation and Reactive Hyperemia

Long-term exposure to ambient air pollution has been associated with cardiovascular morbidity and mortality. Impaired vascular responses may, in part, explain these findings, but the association of such long-term exposure with measures of both conduit artery and microvascular function has not been widely reported. We evaluated the association between residential proximity to a major roadway (primary or secondary highway) and spatially resolved average fine particulate matter (PM2.5) and baseline brachial artery diameter and mean flow velocity, flow-mediated dilation%, and hyperemic flow velocity, in the Framingham Offspring and Third Generation Cohorts. We examined 5,112 participants (2,731 [53%] women, mean age 49 ± 14 years). Spatially resolved average PM2.5 was associated with lower flow-mediated dilation% and hyperemic flow velocity. An interquartile range difference in PM2.5 (1.99 μg/m(3)) was associated with -0.16% (95% confidence interval [CI] -0.27%, -0.05%) lower flow-mediated dilation% and -0.72 (95% CI -1.38, -0.06) cm/s lower hyperemic flow velocity%. Residential proximity to a major roadway was negatively associated with flow-mediated dilation%. Compared with living ≥400 m away, living <50 m from a major roadway was associated with 0.32% lower flow-mediated dilation (95% CI -0.58%, -0.06%), but results for hyperemic flow velocity had wide confidence intervals -0.68 cm/s (95% CI -2.29, 0.93). In conclusion, residential proximity to a major roadway and higher levels of spatially resolved estimates of PM2.5 at participant residences are associated with impaired conduit artery and microvascular function in this large community-based cohort of middle-aged and elderly adults.

COMPARISON OF THE EFFICACY OF BISOPROLOL AND IVABRADINE ON DOPPLER DERIVED CORONARY FLOW RESERVE IN PATIENTS WITH STABLE ANGINA PECTORIS: BEYOND THE HEART RATE

Both beta blockers and ivabradine showed to improve hyperemic coronary flow velocity and coronary flow reserve (CFR) in patients with stable coronary artery disease (CAD). There are no data on comparison of their effects. The purpose of this study was to assess the effects of ivabradine and

Predictive value of brachial reactive hyperemia and flow-mediated dilation in stable coronary artery disease

The purpose of this study was to determine the predictive value of a single measurement of reactive hyperemia (RH) and brachial flow-mediated dilation (FMD) in patients with established stable coronary artery disease (CAD). RH and brachial artery FMD were ultrasonographically measured in 325 patients with stable CAD. Patients were followed for cerebro-cardiovascular events. The median follow-up was 3.7 years (range 0.01-5.7 years). Sixty-seven patients (20.6%) had an cerebro-cardiovascular event. Patients with subsequent events had lower FMD (4.9 ± 3.3% versus 6.3 ± 3.5%, p = 0.003), higher brachial artery resting diameter (5.1 ± 0.7 mm versus 4.8 ± 0.7 mm, p = 0.002) and lower NMD (11.2 ± 5.1% versus 12.8 ± 5.4%, p = 0.02), while the mean hyperemic flow velocity and shear stress did not differ from patients without cerebro-cardiovascular events. Cox proportional hazard model adjusted for sex, age, BMI, and traditional cardiovascular risk factors revealed a hazard ratio of 0.84 for lower FMD (p = 0.01). We conclude that single spot measurements of peak RH do not provide long-term prognostic information, but evaluation of conduit artery FMD predicts long-term cerebro-cardiovascular events in patients with stable CAD. The prognostic value of FMD is incremental to traditional cardiovascular risk factors and may therefore be of clinical importance.

Abstract 18986: Collateral Flow In the Canine Heart Derived From Coronary Wedge Pressure Overestimates Actual Collateral Flow Measured by Fluorescent Microspheres

Purpose: In severe coronary artery disease, coronary collateral flow may prevent distal ischemia. Clinically the ratio between coronary wedge pressure and aortic pressure is used as index of collateral flow. The aim of this study was to validate this method by selective microsphere injections in the LAD during obstruction of LCX flow. Methods: The study was conducted in ten mongrel dogs and was performed in accordance with the Principles of laboratory animal care (NIH) as well as local IACUC. Under anesthesia a thoracotomy was performed and a guide wire equipped with both a pressure and a Doppler velocity sensor was introduced in the LCX. Fluorescent microspheres were injected into the LAD with partial and full occlusions of the LCX. Collateral flow derived from pressure was expressed as the fractional flow reserve, FFRcoll_p calculated according to its definition as; FFRcoll_p = FFRmyo - FFRcor where FFRmyo is the assumed true myocardial FFR. FFRcor_p is zero by definition during full occlusion and unity in the absence of any stenosis resistance. At full occlusion FFRcoll_p equals the ratio between distal wedge pressure, Pw, and aortic pressure Pa. At partial occlusion FFRcoll_p can be calculated from distal pressure, Pd, and Pa by means of the linear FFR model. With microspheres, FFRcoll_m is measured as the ratio between microsphere density in the LCX and that in the LAD perfusion territory but corrected for the estimated contribution of septal 28%, and right, 21%, coronary contribution to LCX collateral flow as derived from literature data. Results: Both, FFRcoll_p and FFRcoll_m were inversely related to the ratio between LCX flow velocity by the maximal hyperemic coronary flow velocity in the LCX. FFRcoll_p overestimated FFR_m at all occlusion degrees by a factor of 3 in average. At full occlusion this difference was significant according to Wilcoxon paired test with P&lt;0.0005. Conclusions: These results show that during severe occlusion pressure-derived measurement of collateral flow overestimates collateral flow as determined from microsphere distributions. Pressure based assessment of collateral flow may thus yield an incorrect estimate of collateral flow.

Abstract 19037: Impact of Stress Hyperglycemia on Coronary Flow Reserve Following Successfully Recanalized Primary Acute Myocardial Infarction in Non-Diabetic Patients

Background: Stress hyperglycemia (SH) is associated with adverse outcome and reduction in myocardial salvage after acute myocardial infarction (AMI), especially in non-diabetic patients. However, no relationship has been identified between admission blood glucose level and coronary flow reserve (CFR) as an index of microvascular function in non-diabetic patients with AMI. Methods: This study assessed 73 consecutive patients with a first anterior AMI who underwent successful percutaneous coronary intervention within 24 h from onset of symptoms. Plasma blood glucose was measured on admission. SH was defined as blood glucose ≥10 mmol/L (180 mg/dl). We excluded the patients with a previous or current diagnosis of diabetes or an abnormal oral glucose tolerance test (OGTT, 75-g) 5 days after admission. CFR was calculated as the ratio of hyperemic, which was induced by intravenous adenosine administration, to baseline diastolic coronary flow velocity of the left anterior descending artery using transthoracic echocardiography 7 days after AMI. Results: In 73 non-diabetic patients (mean age: 65 years, 48 males), 14 patients showed SH (218±48mg/dl). Baseline diastolic coronary flow velocity in patients with SH (24±11cm/s) was higher than those without SH(19±6 cm/s, p=0.04), while there was no significant difference in hyperemic coronary flow velocity between the patients with (50±26 cm/s) and without SH (48±20 cm/s). Calculated CFR of the patients with stress hyperglycemia (2.0±0.4) was significantly lower than those without stress hyperglycemia (2.4±0.6, p=0.02). Conclusions: CFR was impaired in non-diabetic patients with hyperglycemia on admission. Impaired coronary microcirculation may partly contribute to reduced myocardial salvage and adverse outcome in patients with SH.

The Impact of Long-Term Exposure to Air Pollution on Conduit Artery and Microvascular Function

Background: Long-term exposure to ambient air pollution, including fine particulate matter (PM2.5), has been associated with cardiovascular morbidity and mortality. Impaired vascular responses may in part explain these findings, but few studies have examined chronic effects of long-term exposures incorporating measures of both conduit artery and microvascular function in a large population-based study. Aims: We evaluated the impact of residential proximity to primary or secondary highway (&lt;100m, 100-200m, 200-400m, &gt;400m) and long term exposure to PM2.5 (1-year average) on brachial artery flow mediated dilation (FMD) and reactive hyperemia in the Framingham Offspring and Third Generation Cohorts. Methods: FMD (%) and hyperemic flow velocity (cm/s) were assessed in the Offspring 7th (1998-2001) and Third Generation 1st (2001-2005) exams (n=5,133). We evaluated associations between residential proximity to major roads and spatially resolved estimated PM2.5 from land use and satellite images with FMD and hyperemic flow using linear regression. Results: Compared to living further than 400m from a major road, living within 100m was associated with -0.31% (95% CI: -0.53, -0.09) lower FMD and -1.49 cm/s (95% CI: -2.9,- 0.09) lower hyperemic flow velocity in models adjusted for age, sex, body mass index, smoking status, long-term time trends, season, cohort, and indicators of socioeconomic position. A 1 µg/m3 higher average PM2.5 was associated with -0.09% (95% CI: -0.24, 0.06) lower FMD, and -1.07 cm/s (95% CI: -2.0, -0.12) lower hyperemic flow. Results were not materially altered after further adjustment for potential mediators. The magnitude of estimates for hyperemic flow became stronger when we excluded smokers and participants using antihypertensive or lipid-lowering medications. Conclusions: In a large, community-based cohort, measures of long-term exposure to air pollution were associated with impaired conduit and microvascular function.

Impaired coronary flow reserve in dilated cardiomyopathy: lack of tissue microvasculature remodeling

Objective: The aim of this study is to evaluate the cause of CFR impairment in DCM patients by correlating functional CFR assessed and microvascular structural abnormalities measured on endomyocardial biopsy (EMB). Materials and methods: We evaluated EMBs from 26 consecutive DCM patients and EMBs from 11 consecutive Heart Transplant patients. We performed morphometric analysis on EMBs. We measured myocyte mean diameter, capillary density, microvascular remodeling (vessel media area/total vessel area ratio (%)). Coronary flow velocity in the left anterior descending coronary artery was detected by Transthoracic Doppler Echocardiography (TDE) at rest and during adenosine infusion. CFR was the ratio of hyperemic diastolic flow velocity (DFV) to resting DFV. A CFR≤2.5 was considered abnormal. The results were compared to a control group, consisted of 11 heart-transplant (HTx) patients with impaired CFR due to microvascular remodeling. Results: Despite CFR in DCM patients is comparable to the HTx pts (2,25±0,61 vs. 2,0±0,5, p=0.4), microvascular remodeling is significantly lower in DCM pts compared to HTx group (43,93±7,12% vs. 72,3±8,0%, p<0,0001). In DCM patients capillary density (194,83±22,63 vs. 157,2±42,4, p=0,03), fibrosis (19,44±7,55% vs. 6,8±5,0%, p<0,02) and myocyte mean diameter (23,79±3,01μm vs. 20,5±3,7μm, p=0,5) are significantly higher than in HTx group. In DCM patients CFR shows a significant inverse correlation with central venous pressure (r= -0,692, p=0,02), with right heart pressure (r= -0,609, p=0,05) and with NTproBNP (r= -0,754, p=0,01) and a positive correlation with cardiac output (r=0,737, p=0,01) and oxygen consumption (r=0,412, p=0,02). Conclusion: CFR impairment in DCM patients is not related to microvascular remodeling. It is closely related to cardiac performance and the patient's clinical status. Patients with pathological CFR (CFR<2,5) have a poorer prognosis, since they have worsen clinical and hemodynamic conditions.

Non-invasively assessed coronary flow reserve stratifies outcomes in patients with intermediate left main coronary artery stenosis

Background: Correct assessment of the significance of left main coronary artery (LMCA) stenosis on the basis of clinical and angiographic information alone often cannot be done reliably and requires assessment of functional significance of lesions observed on coronary angiography. Aim: The aim of this study was to determine the prognostic value of noninvasively measured coronary flow reserve (CFR) in patients with angiographically assessed intermediate or equivocal LMCA stenosis during long-term follow up. Methods: Hundred patients (59±9 years, 80 male) in whom LMCA was assessed by coronary angiography to be ≤50% diameter stenosis; without significant left anterior descending artery stenosis (LAD), were included in this prospective follow-up study. All patients underwent transthoracic Doppler echocardiography measurements of CFR in medial part of LAD after intravenous adenosine administration to assess functional significance of LMCA stenosis. CFR values were calculated as the ratio between hyperemic maximal flow velocity and resting flow velocity. Patients were followed for the mean period of 27±10 months for the occurrence of composite end point including cardiovascular death, myocardial infarction, hospitalization due to unstable angina and clinically guided revascularization. Results: 91 patient completed follow-up. Events occurred in 16. Mean CFR value of 1.80±0.44 for patients having events was significantly lower, compared to those who were free of events where mean CFR value was 2.4±0.44 (p<0.001). During the follow up period (range 1-50 months), 69 patients (95, 8%) with CFR ≥2 remained free of death and major adverse events vs. 6 patients (31,6%) with CFR <2, p<0.001. By Kaplan-Meier method, at 24 months the percent estimated survival free from cardiac related events was 95±3% in patients with CFR ≥2 and 45±11% in patients with CFR <2, p<0.001. Picture Conclusion: In patients with intermediate or equivocal left main coronary artery disease, CFR ≥2 is associated with low event rate and excellent survival. According to our results CFR measured by transthoracic Doppler echocardiography provides reliable and precise, yet non-invasive tool for the assessment of functional severity of LMCA disease that carries significant prognostic information in long-term follow-up.

Coronary microvascular dysfunction in patients with acromegaly: a hint for their increased cardiovascular risk

Purpose: Acromegaly (AC) increases the risk of cardiovascular diseases. We evaluated Coronary Flow Reserve (CFR) by Transthoracic Doppler Echocardiography (TDE), as an index of coronary microvascular function, in AC. Methods: 39 AC patients (pts) (22 M, aged 52±11 years) without clinical evidence of heart disease, and 48 controls matched for age and gender were studied. 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. The median time between the onset of symptoms and CFR assessment was 5 years (interquartile range 2-10 years). Results: In AC pts, CFR was lower than in controls (2.9±0.8 vs 3.8±0.7, p<0.0001) (Figure A). CFR was ≤2.5 in 13 (33.3%) pts compared with controls (0%) (p<0.0001). CFR was inversely related to insulin-like growth factor 1 (IGF-1) levels (Figure B). In pts with CFR≤2.5, IGF-1 was higher (756 [381-898] vs 246 [186-484] mg/L, p<0.004) while growth hormone (GH) levels were similar (6.3 [2.8-13.7] vs 5 [2.8-8.9] mg/L, p=0.8). At multivariable analysis adjusted for age, gender and other cardiovascular risk factors, IGF-1 was an independent determinant of CFR (b=-0.527, p<0.0001) and a predictor of CFR≤2.5 (p=0.01). ![Figure][1] CFR in acromegaly and relation with IGF Conclusions: Microvascular function is impaired in AC and is correlated with IGF-1 independently of GH levels, suggesting a negative effect of IGF-1 on coronary microcirculation that may contribute to the increased cardiovascular risk in AC. [1]: pending:yes

Value of admission glucose to predict impaired coronary microcirculation in acute ST-elevation myocardial infarction

Background: Acute hyperglycemia is frequently observed in non-diabetic ST-elevation myocardial infarction (STEMI) patients. It is thought to be associated with the release of stress-mediators like noradrenalin and cortisol, which antagonize insulin and promote glycogenolysis and hyperglycemia, or with the high incidence of impaired glucose tolerance among STEMI patients. Hyperglycemia recently was shown to be associated with the no-reflow phenomenon, which is mainly a manifestation of microvascular dysfunction. We recently showed that no-reflow (or not achieving TIMI 3 flow) with primary PCI for STEMI had independent prognostic value with regard tot 30-day, as well as 1-year mortality, next to admission glucose. Although no reflow in this study was an indirect measure of microvascular dysfunction, the significant association between no-reflow and increasing admission glucose and the attenuation of the effect of no-reflow by glucose concentration in multivariate analysis indicate the role of acute hyperglycemia in the pathophysiology of microvascular dysfunction. Methods: In 76 patients with a first anterior wall STEMI, baseline and minimal microvascular resistance in IRAs and non-IRAs immediately after reperfusion and at 1-week and 6-month follow-up were calculated as the ratio of mean transvascular pressure gradient to mean baseline and to adenosine-induced hyperemic blood flow velocity, respectively. Patients were divided in two groups, glucose below 11.0 mmol/L (group A) and glucose equal or higher than 11 mmol/L (group B), according to a cut-off level of the American Diabetes Association and the Euro Heart Survey. Results: Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.75 to 4.89 mm Hg cm-1 s-1) and was significantly higher in group B than in group A immediately after reperfusion and at 1-week. Conclusion: In conclusion, minimal microvascular resistance is higher in anterior STEMI patients with hyperglycemia equal or above 11.0 mmol/L compared to patients with glucose leven lower than 11.0 mmol/L. Hyperglycemia in STEMI patients could prove to be an important predictor of microvacular dysfunction and obstruction.

Coronary flow reserve and functional improvement after resynchronization therapy

Objective: The aim of the study was to evaluate the relation of coronary flow reserve (CFR) with left ventricular functional improvement after cardiac resynchronization therapy (CRT). Background: In patients with non-ischemic dilated cardiomyopathy, CFR is related to microvascular function and viability. Abnormal CFR <2, has been shown to be independent predictor of bad prognosis. Method: Forty one patient (mean age 60±10 years, male 38) with heart failure (EF 26±5%) and QRS duration of 159±22ms underwent CFR measurement with transthoracic Doppler echocardiography before CRT implantation, during hyperemia induced with adenosine. CFR was calculated as a ratio of hyperemic and basal flow velocities. Responders were defined by decrease in end-systolic volume (ESV) ≥15%, 6 months after CRT implantation. Results: At inclusion, left ventricular ejection fraction (EF), end-systolic volume, end-diastolic volume, QRS duration, 6 min walk test and coronary flow velocity at rest did not differ in responder vs. nonresponder group (p=ns). Before CRT implantation, responders showed a greater increase in coronary flow velocities during hyperemia, and consequently higher CFR: 2.23±0.59 vs. 1.67±0.54 (p=0.010). We found significant correlation between CFR before CRT and EF improvement after 6 months (r=0.492, p=0.008). End systolic and end diastolic diameters, left bundle branch block (LBBB), and CFR before CRT were predictors of LV functional recovery. By multivariate analysis, only CFR before CRT and LBBB were independent predictors of left ventricular recovery in the follow-up period (p=0.011). Conclusion: We have found that adequate CFR response, which means preserved coronary microcirculation and LBBB, as an ECG surrogate of dyssynchrony were independent predictors of LV reverse remodeling.

Thoracic periaortic and visceral adipose tissue and their cross‐sectional associations with measures of vascular function

ObjectivePerivascular fat may have a local adverse effect on the vasculature. We evaluated whether thoracic periaortic adipose tissue (TAT), a type of perivascular fat, and visceral adipose tissue (VAT) are associated with vascular function.Design and MethodsTAT and VAT were quantified in Framingham Heart Study participants using multidetector computed tomography; vascular function was assessed using brachial artery vasodilator function, peripheral arterial tone and arterial tonometry (n= 2735, 48% women, mean age 50 years, mean BMI 27.7 kg/m2). Using multiple linear regression, we examined relations between TAT, VAT, and vascular measures while adjusting for cardiovascular risk factors.ResultsMean TAT and VAT volumes were 13.2 and 1763 cm3. TAT and VAT were associated with multiple vascular function measures after multivariable adjustment. After BMI adjustment, TAT and VAT remained negatively associated with peripheral arterial tone and inverse carotid femoral pulse wave velocity (p<0.02); TAT was negatively associated with hyperemic mean flow velocity (p=0.03). Associations of TAT with vascular function were attenuated after VAT adjustment (all p>0.06).ConclusionThoracic periaortic and visceral fat are associated with microvascular function and large artery stiffness after BMI adjustment. These findings support the growing recognition of associations between ectopic fat and vascular function.

Regional Difference of Microcirculation in Patients with Asymmetric Hypertrophic Cardiomyopathy: Transthoracic Doppler Coronary Flow Velocity Reserve Analysis

To evaluate, by noninvasive coronary flow velocity reserve (CFVR), whether patients with asymmetric hypertrophic cardiomyopathy (HC), with or without left ventricular outflow tract obstruction, demonstrate significant regional differences of CFVR. We evaluated 61 patients with HC (27 men; mean age 49 ± 16 years), including 20 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 41 patients without obstruction (HCM). The control group included 20 age- and sex-matched subjects. Transthoracic Doppler echocardiography CFVR of the left anterior descending coronary artery (LAD) and the posterior descending coronary artery (PD) were performed, including calculation of relative CFVR as the ratio between CFVR LAD and CFVR PD. Compared with the controls, all the patients with HC had lower CFVR LAD (2.12 ± 0.53 vs 3.34 ± 0.67; P < .001) and CFVR PD (2.29 ± 0.49 vs 3.21 ± 0.65; P < .001). CFVR LAD in HOCM group in comparison with the HCM group was significantly lower (1.93 ± 0.42 vs 2.22 ± 0.55; P = .047), due to higher basal diastolic coronary flow velocities (0.40 ± 0.09 vs 0.33 ± 0.07 m/sec; P = .002), with similar hyperemic diastolic flow velocities (0.71 ± 0.16 vs 0.76 ± 0.19 m/sec; P = .330), respectively. There was no significant difference in CFVR PD between patients with HOCM and those with HCM (2.33 ± 0.46 vs 2.27 ± 0.50; P = .636), respectively. Relative CFVR was lower in the HOCM group compared with the HCM group (0.84 ± 0.16 vs 0.98 ± 0.14; P = .001). By multivariable regression analysis, left ventricular outflow tract gradient was the independent predictor of CFVR LAD (B = -0.24; P = .008) and relative CFVR (B = -0.34; P = .016). CFVR LAD and relative CFVR were significantly lower in patients with HOCM compared with patients with HCM. Regional differences of CFVR are present only in patients with significant left ventricular outflow tract obstruction, which suggests that obstruction per se, by increasing wall stress in basal conditions, leads to higher basal diastolic coronary flow velocities and results in lower CFVR in LAD compared with PD.

055 RELIABILITY OF RESTING CORONARY HAEMODYNAMICS WHEN REPEATED AFTER 6 MONTHS

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 hyperaemic 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 (140 µg/kg/min). Measurements were repeated after 6 months at the same vessel location. Changes in coronary flow velocity and microcirculatory resistance were compared using Student t test and the F test. Results Mean flow velocity at rest was similar at baseline and 6 months (22.2±8.5 cm/s vs 21.6±8.5 cm/s, p=0.78); hyperaemic mean flow (43.3±14.1 cm/s vs 46.5±11.5 cm/s, p=0.47) similarly did not significantly change. The mean change between baseline and 6 months was 4% and 17% for resting and hyperaemic flow respectively and this was not significantly different (p=0.27). Peak coronary flow velocity was also similar at both time points at rest (53.5±27.2 cm/s vs 46.9±20.3 cm/s, p=0.38) and hyperaemia (88.0±22.5 cm/s vs 90.4±24.6 cm/s, p=0.75); the mean change was 3.0% and 9.0% respectively (p=0.50). Microcirculatory resistance measured at rest was unchanged between baseline and 6 months at rest (4.97±2.37 mm Hg/cm.s vs 5.23±2.25 mm Hg/cm.s, p=0.58) and during hyperaemia (1.94±0.72 vs 1.95±0.67, p=0.98). The mean change in resistance was 17.8% at rest and 11.9% for hyperaemia, with no significant difference (p=0.64). Conclusions Coronary flow velocity and microcirculatory resistance when measured over rest or hyperaemia, vary to a similar degree over 6 months. This suggests that coronary haemodynamics during resting conditions are stable, consistent and reproducible in a manner similar to that observed during adenosine-mediated hyperaemia.

Arginase inhibition improves coronary microvascular function and reduces infarct size following ischaemia–reperfusion in a rat model

Ischaemia-reperfusion injury is associated with reduced bioavailability of nitric oxide (NO) and microvascular dysfunction. One emerging mechanism behind reduced NO bioavailability is upregulation of arginase, which metabolizes the NO synthase substrate l-arginine. This study investigated the effects of arginase inhibition on coronary flow velocity and infarct size during reperfusion. Anaesthetized rats, subjected to 30-min coronary artery ligation and reperfusion up to 8 days, were treated with vehicle or the arginase inhibitor N(ω) -hydroxy-nor-l-arginine (nor-NOHA; 100 mg kg(-1) ) intravenously 15 min before ischaemia. Coronary flow velocity was determined repeatedly during reperfusion. Arginase activity in the ischaemic-reperfused myocardium was increased already at 20 min of reperfusion and maintained at 8 days. Infarct size was reduced by arginase inhibition at 2 h (39 ± 3% of the area at risk (AAR) vs. 51 ± 2% in the vehicle group, P < 0.01) and at 8 days of reperfusion (13 ± 2% of the left ventricle (LV) vs. 22 ± 2%, P < 0.05). Basal coronary flow velocity was higher during reperfusion in the group given nor-NOHA, and it correlated inversely to infarct size (P < 0.01, r = -0.60). Hyperaemic coronary flow velocity was also increased in the nor-NOHA-treated group compared to vehicle at 24 h and at day 8 (P < 0.05). It is concluded that arginase activity is increased already during early reperfusion. Arginase inhibition increases coronary flow velocity and reduces infarct size that is sustained 8 days after reperfusion. Inhibition of arginase may thus be a promising therapeutic target to prevent the development of microvascular dysfunction and myocardial injury following ischaemia-reperfusion.

Pathological Substrates of Impaired Coronary Flow Reserve in Dilated Cardiomyopathy and Heart Transplant Patients

Purpose The aim of this study is to evaluate the cause of CFR impairment in DCM patients by correlating functional CFR assessed and microvascular structural abnormalities measured on endomyocardial biopsy (EMB). Methods and Materials We evaluated EMBs from 26 consecutive DCM patients and EMBs from 11 consecutive Heart Transplant patients. We performed morphometric analysis on EMBs. We measured myocyte mean diameter, capillary density, microvascular remodeling (vessel media area/total vessel area ratio (%)). Coronary flow velocity in the left anterior descending coronary artery was detected by Transthoracic Doppler Echocardiography (TDE) at rest and during adenosine infusion. CFR was the ratio of hyperemic diastolic flow velocity (DFV) to resting DFV. A CFR≤2.5 was considered abnormal. The results were compared to a control group, consisted of 11 heart-transplant (HTx) patients with impaired CFR due to microvascular remodeling. Results Despite CFR in DCM patients is comparable to the HTx pts (2,25 ± 0,61 vs. 2,0 ± 0,5, p=0.4), microvascular remodeling is significantly lower in DCM pts compared to HTx group (43,93 ± 7,12% vs. 72,3 ± 8,0%, p Conclusions CFR impairment in DCM patients is not related to microvascular remodeling. It is closely related to cardiac performance and the patient’s clinical status. Patients with pathological CFR (CFR