Coronary Flow Reserve Ratio Research Articles

5879Coronary microvascular dysfunction is associated with poor glycemic control in women with diabetes presenting with chest pain and non-obstructive coronary artery disease

Abstract Background Patients with type 2 diabetes are at an increased risk of cardiovascular events compared to individuals without diabetes. The role glycemic control plays in reducing cardiovascular risk remains uncertain. Coronary microvascular dysfunction (CMD) is more frequent in women compared to men, is prevalent in patients with type 2 diabetes and is linked to adverse cardiovascular events. We compared the association between CMD and glycemic control across sexes in patients with chest pain and non-obstructive coronary artery disease (CAD). Methods Patients with chest pain who were found to have non-obstructive CAD (stenosis <40%) at angiography underwent an invasive assessment of endothelial-independent and endothelial–dependent coronary microvascular function. Using a Doppler guidewire, endothelial-independent microvascular function was assessed by measuring the coronary flow velocity in response to intracoronary adenosine and comparing this to baseline to calculate the coronary flow reserve ratio (CFRAdn). A CFRAdn ≤2.5 was considered abnormal. Endothelial-dependent microvascular function was assessed by measuring the percent change in coronary blood flow in response to intracoronary infusions of acetylcholine (%ΔCBFAch), with a %ΔCBFAch ≤50% considered abnormal. Patients were classified as having normal versus abnormal CFRAdn and %ΔCBFAch. Measurements of HbA1c and fasting serum glucose were obtained at the time of catheterization and compared between groups after stratification by sex. Results Between 1993 and 2012, 1,469 patients (mean age 50.4 years, 35% male) underwent coronary angiography and invasive testing for CMD, of which 129 (8.8%) had type 2 diabetes. Fifty one (39.5%) had an abnormal %ΔCBFAch and 49 (38.0%) had an abnormal CFRAdn. Conventional cardiovascular risk factors did not vary significantly between groups. Females with an abnormal CFRAdn or abnormal %ΔCBFAch had a significantly higher HbA1c compared to those with a normal CFRAdn or %ΔCBFAch respectively: HbA1c % (standard deviation) 7.4 (2.1) vs. 6.5 (1.1), p=0.035 and 7.3 (1.9) vs. 6.4 (1.2), p=0.022, respectively. Females with an abnormal CFRAdn had significantly higher fasting serum glucose concentrations compared to those with a normal CFRAdn: fasting serum glucose mg/dL (standard deviation) 144.4 (55.6) vs. 121.9 (28.1), p=0.035. These effects were not observed in men. Amongst female diabetics, a higher HbA1c was significantly associated with any CMD after adjusting for covariates: odds ratio (95% confidence interval) 1.69 (1.01 – 2.86) p=0.049; and a fasting serum glucose >140 mg/dL was significantly associated with an abnormal CFRAdn, 4.28 (1.43–12.81). Conclusion Poor glycemic control is associated with CMD in females with diabete who present with chest pain and non-obstructive CAD. These findings highlight the importance of sex-specific risk stratification models and treatment strategies when managing cardiovascular risk in diabetics. Acknowledgement/Funding Mayo Foundation

Coronary microvascular dysfunction is associated with poor glycemic control amongst female diabetics with chest pain and non-obstructive coronary artery disease

BackgroundPatients with type 2 diabetes mellitus are at an increased risk of adverse cardiovascular events compared to those without diabetes. The timing, relative to disease onset, and degree of glycemic control that reduces the risk of adverse cardiovascular events remains uncertain. Coronary microvascular dysfunction is prevalent in patients with type 2 diabetes mellitus and is linked to adverse cardiovascular events. We assessed the association between endothelial-dependent and endothelial-independent coronary microvascular dysfunction and glycemic control in patients presenting with chest pain and nonobstructive coronary disease at angiography.MethodsPatients presenting with chest pain and found to have non-obstructive CAD (stenosis < 40%) at angiography underwent an invasive assessment of endothelial-independent and endothelial –dependent microvascular function. Endothelial-independent microvascular function was assessed by comparing the coronary flow velocity, measured using a Doppler guidewire, in response to intracoronary infusion of adenosine to calculate the coronary flow reserve ratio in response to adenosine (CFRAdn Ratio). A CFRAdn Ratio ≤ 2.5 was considered abnormal. Endothelial-dependent microvascular function was assessed by measuring the percent change in coronary blood flow in response to intracoronary infusions of acetylcholine (%ΔCBFAch), and microvascular endothelial dysfunction defined as a %ΔCBFAch of ≤ 50%. Patients were classified by normal versus abnormal CFRAdn Ratio and %ΔCBFAch. Measurements of HbA1c and fasting serum glucose were obtained prior to catheterization and compared between groups.ResultsBetween 1993 and 2012, 1469 patients (mean age 50.4 years, 35% male) underwent coronary angiography and invasive testing for coronary microvascular dysfunction, of which 129 (8.8%) had type 2 diabetes. Fifty-one (39.5%) had an abnormal %ΔCBFAch and 49 (38.0%) had an abnormal CFRAdn Ratio. Conventional cardiovascular risk factors and cardiovascular or diabetic medication use did not vary significantly between groups. Females with an abnormal CFRAdn Ratio or abnormal %ΔCBFAch had a significantly higher HbA1c compared to patients with a normal CFRAdn Ratio or %ΔCBFAch respectively: HbA1c % (standard deviation) 7.4 (2.1) vs. 6.5 (1.1), p = 0.035 and 7.3 (1.9) vs. 6.4 (1.2), p = 0.022, respectively. Female patients with an abnormal CFRAdn Ratio had significantly higher fasting serum glucose concentrations compared to those with a normal CFRAdn Ratio: fasting serum glucose mg/dL (standard deviation) 144.4 (55.6) vs. 121.9 (28.1), p = 0.035. This was not observed in men. Amongst female diabetics, a higher HbA1c was significantly associated with any coronary microvascular dysfunction both in a univariate and multivariate analysis: odds ratio (95% confidence interval) 1.69 (1.01–2.86) p = 0.049; and a fasting serum glucose > 140 mg/dL was significantly associated with an abnormal CFRAdn Ratio, 4.28 (1.43–12.81).ConclusionPoor glycemic control is associated with coronary microvascular dysfunction amongst female diabetics presenting with chest pain and non-obstructive CAD. These findings highlight the importance of sex specific risk stratification models and treatment strategies when managing cardiovascular risk amongst diabetics. Further studies are required to identify additional risk prevention tools and therapies targeting microvascular dysfunction as an integrated index of cardiovascular risk.

P1712Diagnostic performance of coronary flow reserve ratio for the detection of coronary artery disease on 13N-ammonia positron emission tomography

P1712Diagnostic performance of coronary flow reserve ratio for the detection of coronary artery disease on 13N-ammonia positron emission tomography

Clinical Usefulness of Coronary Flow Reserve Ratio for the Detection of Significant Coronary Artery Disease on &lt;sup&gt;13&lt;/sup&gt;N-Ammonia Positron Emission Tomography

This study aimed to evaluate the diagnostic performance of coronary flow reserve (CFR), hyperemic myocardial blood flow (hMBF), and CFR ratio for detecting significant coronary artery disease (CAD) on 13N-ammonia positron emission tomography (PET).Methods and Results:We analyzed 63 patients (mean age, 71±9 years; 43 males) with suspected CAD who underwent both pharmacological stress/rest 13N-ammonia PET and coronary angiography. CFR and hMBF for PET were calculated automatically using quantitative PET software, and the CFR ratio was defined as the ratio of per-vessel CFR to maximum CFR in a standard 17-segment model. We compared the diagnostic performance among the 3 quantitative values. In the per-vessel analysis, 55 vessels were diagnosed as significant CAD (≥70% stenosis and/or fraction flow reserve ≤0.8). CFR, hMBF, and CFR ratio of significant CAD were significantly lower than for non-significant CAD (1.85±0.69 vs. 2.38±0.69; P<0.01, 1.67±0.54 vs. 2.19±0.52 mL·min-1·g-1; P<0.01, and 0.66±0.15 vs. 0.82±0.09; P<0.01, respectively). In the receiver-operating characteristic curve analysis, CFR, hMBF, and CFR ratio had areas under the curve of 0.71, 0.75, and 0.85 respectively, and the CFR ratio was significantly higher than CFR and hMBF (P<0.05). The sensitivity, specificity, and accuracy of the CFR ratio with an optimal cutoff value of 0.75 were 75%, 85%, and 82%, respectively. Clinically, the CFR ratio in 13N-ammonia PET was more effective in detecting significant CAD.

CYP2C19 variants and epoxyeicosatrienoic acids in patients with microvascular angina

BackgroundCategorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the impact of CYP2C19 polymorphisms and EETs on the patients with microvascular angina (MVA) caused by coronary microvascular dysfunction. Methods and resultsWe examined CYP2C19 genotypes in patients with MVA (n=81). MVA was defined as absence of coronary artery stenosis and epicardial spasms, and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite.In MVA, the patients with CYP2C19 PM were 34.6% and high sense C-reactive protein (hs-CRP) levels in CYP2C19 PM were significantly higher than that of non-PM group (0.165±0.116 vs. 0.097±0.113mg/dL, P=0.026). Moreover, DHET levels in CYP2C19 PM were significantly lower than that of non-PM (10.4±4.58 vs. 15.6±11.1ng/mL, P=0.003 (11,12-DHET); 12.1±3.79 vs. 17.3±6.49ng/mL, P=0.019 (14,15-DHET)). ConclusionsThe decline of EET owing to CYP2C19 variants may affects coronary microvascular dysfunction via chronic inflammation.

Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina.

Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the association of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. We examined CYP2C19 genotypes in patients with MVA (n = 71) and healthy subjects as control (n = 71). MVA was defined as the absence of coronary artery stenosis and epicardial spasms and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P = 0.007) and high sense C-reactive protein (hs-CRP) levels (0.127 ± 0.142 vs. 0.086 ± 0.097 mg/dl; P = 0.043) than those of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180 ± 0.107 vs. 0.106 ± 0.149 mg/dl, P = 0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP, and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM [10.9 ± 1.64 vs. 14.2 ± 5.39 ng/ml, P = 0.019 (11,12-DHET); 15.2 ± 4.39 vs. 17.9 ± 4.73 ng/ml, P = 0.025 (14,15-DHET)]. CYP2C19 variants are associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction.

Sex differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder.

Categorization as a cytochrome P-450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. It is correlated with an increase in the circulating levels of high-sense C-reactive protein (hs-CRP) in women only, although its role in coronary microcirculation is unclear. We examined sex differences in the impact of the CYP2C19 genotype and low-grade inflammation on coronary microvascular disorder (CMVD). We examined CYP2C19 genotypes in patients with CMVD (n = 81) and in healthy subjects as control (n = 81). CMVD was defined as the absence of coronary artery stenosis and epicardial spasms, the presence of inverted lactic acid levels between the intracoronary and coronary sinuses, or an adenosine triphosphate-induced coronary flow reserve ratio < 2.5. CYP2C19 PMs have two loss-of-function (LOF) alleles (*2, *3). Extensive metabolizers have no LOF alleles, and intermediate metabolizers have one LOF allele. The ratio of CYP2C19 PM and hs-CRP levels in CMVD was significantly higher than that of controls, especially in women (40.9 vs. 13.8%, P = 0.013; 0.11 ± 0.06 vs. 0.07 ± 0.04 mg/dl, P = 0.001). Moreover, in each CYP2C19 genotype, hs-CRP levels in CMVD in CYP2C19 PMs were significantly higher than those of the controls, especially in women (0.15 ± 0.06 vs. 0.07 ± 0.03, P = 0.004). Multivariate analysis for CMVD indicated that the female sex, current smoking, and hypertension were predictive factors, and that high levels of hs-CRP and CYP2C19 PM were predictive factors in women only (odds ratio 3.5, 95% confidence interval 1.26-9.93, P = 0.033; odds ratio 4.1, 95% confidence interval 1.15-14.1, P = 0.038). CYP2C19 PM genotype may be a new candidate risk factor for CMVD via inflammation exclusively in the female population.

Coronary microvascular dysfunction is associated with baseline QTc prolongation amongst patients with chest pain and non-obstructive coronary artery disease

BackgroundCoronary microvascular dysfunction (CMD) causes ischemia and is linked to adverse cardiovascular events. Acute transmural ischemia is associated with QT prolongation, but whether CMD affects repolarization is unknown. The aim of this study was to determine if CMD is associated with prolongation of resting heart rate corrected QT interval (QTc). MethodsIn patients presenting to the catheterization laboratory with chest pain and non-obstructive coronary artery disease (CAD) at angiography, coronary flow reserve (CFR) in response to intracoronary adenosine was measured and compared to baseline to give a CFR ratio. The Bazett’s-derived QTc was manually derived from patients’ 12-lead ECG obtained prior to the procedure. QTc was compared between patients with normal and abnormal (CFR ratio≤2.5) coronary microvascular function. ResultsOf the 926 patients included in this study, 281 patients (30%) had CMD (mean age 53.2years [SD 12.7], 25% male). QTc was significantly longer in those with an abnormal CFR response to adenosine (median [Q1, Q3] ms: 420 [409, 438] vs. 416 [405, 432]; p value<0.001) and patients in the lowest quartile of CFR had a significantly longer QTc compared to those in the highest quartile (median [Q1, Q3] ms: 420 [409, 439] vs. 413 [402, 426]; p<0.001). In a linear regression model adjusting for age and sex, CMD was associated with an increase in QTc of 3.09ms (p=0.055). ConclusionOur data suggest that CMD may be associated with an increase in baseline QTc, however the precise clinical relevance of this finding needs to be better investigated in larger clinical studies.

Coronary Flow Reserve, Strain and Strain Rate Imaging during Pharmacological Stress before and after Percutaneous Coronary Intervention: Comparison and Correlation

Coronary flow reserve (CFR) could apply reliable information about the coronary circulation, and strain (S) and strain rate imaging (SRI) are able to quantify the left ventricular myocardial performance. The aim of this study was to assess myocardial performance in relation to the function of the coronary circulation before and after successful percutaneous coronary intervention (PCI) of the left anterior descending artery. Fourteen patients (10 men, 4 women, mean age 53.2 ± 11.4 years) with severe left anterior descending stenosis who had a successful selective PCI were recruited into this study. CFR and myocardial deformity indices (S and SR) were recorded before and after percutaneous intervention, both at rest and during stress echo test. CFR, S, and SR increased after intervention significantly. There was significant correlation between CFR ratio and poststress systolic strain (SS) ratio and early diastolic strain rate (ESR) ratio (P < 0.05 and r > 0.6). Also CFR improvement had significant relationship with changes of poststress Systolic SR and poststress Systolic S (P < 0.05 and r > 0.6). Based on regression analysis the amount of change in CFR was independently associated with change in SS during stress and systolic SR. PCI improves CFR (a marker of coronary perfusion), strain, and strain rate (markers of regional cardiac wall deformation). The independent association between CFR improvement and poststress systolic strain and strain rate means that SRI parameters can independently predict CFR changes after PCI.

Coronary vasoreactivity is not altered in young people with type 1 diabetes

Background and aim Abnormal coronary microvascular circulation has been demonstrated in diabetes and is associated with increased rate of cardiovascular events. Our objective was to evaluate coronary vasoreactivity in young people with type 1 diabetes with and without microvascular complications. Methods and results Twenty-five type 1 diabetic patients without microvascular complications (DC–), 23 with microvascular complications (DC+), and 18 control subjects (C) were studied. Coronary vasoreactivity was assessed by means of coronary flow reserve (CFR). Blood flow velocity in the left anterior descending coronary artery was measured at rest and after high-dose dipyridamole using transthoracic color-guided pulsed Doppler echocardiography. CFR was defined as the ratio of hyperaemic to resting diastolic peak flow velocities. The three groups had similar cardiac function parameters, and also systolic and diastolic blood pressure at rest, which remained unchanged during dipyridamole infusion. Resting coronary flow velocity was comparable in C, DC–, and DC+ ( p = ns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69 ± 0.16 m/s), DC– (0.69 ± 0.18 m/s), and DC+ (0.66 ± 0.11 m/s). Mean CFR ratio was similar in C (3.33 ± 0.66), DC– (3.30 ± 0.51), and DC+ (3.24 ± 0.60). At multiple linear regression analysis, no association was found between CFR and age, sex, HbA 1c, duration of diabetes, and complications. Conclusion Coronary vasodilatory function is preserved in young D patients, even those with early microvascular complications, suggesting that coronary vasoreactivity deteriorates at more advanced stages of microvascular complications and/or in the presence of other cardiovascular risk factors.

Lack of Correlation Between Noninvasive Stress Tests and Invasive Coronary Vasomotor Dysfunction in Patients With Nonobstructive Coronary Artery Disease

Despite a nonobstructive coronary angiogram, many patients may still have an abnormal coronary vasomotor response to provocation and to myocardial demand during stress. The ability of noninvasive stress tests to predict coronary vasomotor dysfunction in patients with nonobstructive coronary artery disease is unknown. All patients with nonobstructive coronary artery disease who had invasive coronary vasomotor assessment and a noninvasive stress test (exercise ECG, stress echocardiography, or stress nuclear imaging) within 6 months of the cardiac catheterization with provocation at our institution were identified (n=376). Coronary vasomotor dysfunction was defined as a percentage increase in coronary blood flow of <or=50% to intracoronary acetylcholine (endothelium-dependent dysfunction) and/or a coronary flow reserve ratio of <or=2.5 to intracoronary adenosine (endothelium-independent dysfunction). We determined the sensitivity and specificity of various noninvasive stress tests to predict coronary vasomotor dysfunction in these patients. On invasive testing, 233 patients (63%) had coronary vasomotor dysfunction, of which 187 patients (51%) had endothelium-dependent dysfunction, 109 patients (29%) had endothelium-independent dysfunction, and 63 patients (17%) had both. On noninvasive stress testing, 157 (42%) had a positive imaging study and 56 (15%) a positive ECG stress test. The noninvasive stress tests had limited diagnostic accuracy for predicting coronary vasomotor dysfunction (41% sensitivity [95% CI, 34 to 47] and 57% specificity [95% CI, 49 to 66]), endothelium-dependent dysfunction (41% sensitivity [95% CI, 34 to 49] and 58% specificity [95% CI, 50 to 65]), or endothelium-independent dysfunction (46% sensitivity [95% CI, 37 to 56] and 61% specificity [95% CI, 54 to 67]). The exercise ECG test was more specific but less sensitive than the imaging tests. This study suggests that a negative noninvasive stress test does not rule out coronary vasomotor dysfunction in symptomatic patients with nonobstructive coronary artery disease. This underscores the need for invasive assessment or novel more sensitive noninvasive imaging for these patients.

Coronary flow reserve and heart failure in experimental coxsackievirus myocarditis. A transthoracic Doppler echocardiography study

The objective of this study was to apply transthoracic Doppler echocardiography (TTDE) in mice to study coronary flow reserve (CFR), an index of coronary microvascular function, in mild and severe forms of experimental viral myocarditis. Regarding methodology, BALB/c mice were infected with cardiotropic coxsackieviruses causing either a mild (Nancy strain) or a severe (Woodruff strain) myocarditis. Left ventricular dimensions, fractional shortening, and CFR (ratio of left coronary artery flow velocity during maximal adenosine-induced vasodilatation to rest) were measured by TTDE before infection and again 1 or 2 wk after infection. As a result, the resting flow velocity did not change after infection. In contrast, CFR reduced significantly 1 wk after infection with either virus variant [from 2.5 (SD 0.3) to 1.4 (SD 0.1) in severe and from 2.4 (SD 0.4) to 2.1 (SD 0.3) in mild myocarditis], being significantly lower in the severe than mild myocarditis. CFR remained low in severe myocarditis 2 wk after infection. Fractional shortening decreased to the same levels 1 wk after infection with either virus variant [from 0.54 (SD 0.02) to 0.43 (SD 0.03) in severe and from 0.51 (SD 0.03) to 0.44 (SD 0.02) in mild myocarditis, P < 0.05]. However, 2 wk after infection, mice with severe myocarditis had enlarged left ventricles and lower fractional shortening [0.31 (SD 0.03)] than mice with mild myocarditis [0.47 (SD 0.02), P < 0.01]. In conclusion, CFR measured with TTDE is reduced in coxsackievirus myocarditis in mice. Low CFR is associated with progressive heart failure, indicating that dysfunction of coronary microcirculation is a determinant of poor outcome in viral myocarditis.

Contrast-enhanced transthoracic second harmonic echo doppler with adenosine: A noninvasive, rapid and effective method for coronary flow reserve assessment

OBJECTIVESThe purpose of this study is to evaluate the feasibility in detecting blood flow in the left anterior descending coronary artery (LAD) using transthoracic color Doppler (CD) imaging (in both second harmonic and fundamental mode) along with contrast enhancement and to verify if this new noninvasive method along with adenosine is safe, rapid and effective in assessing coronary flow reserve (CFR).BACKGROUNDFeasibility of contrast-enhanced transthoracic Doppler recording (in both second harmonic and fundamental mode) of blood flow velocity in the LAD has not been assessed. Adenosine has a greater vasodilator potency and more favorable kinetics than dipyridamole and thus it can be more suitable for assessing CFR in conjunction with this method.METHODSSixty-one patients with angiographically patent LAD underwent CD (both in fundamental and harmonic mode) as well as color-guided pulsed wave (PW) Doppler recording of blood flow velocity in the distal LAD before and after intravenous contrast injection. A second group of patients (n = 77), undergoing coronary angiography, was submitted to transthoracic contrast-enhanced PW Doppler recording of blood flow velocity in the LAD using harmonic CD as a guide, at rest and during adenosine-induced hyperemia.RESULTSHarmonic CD along with echo contrast consistently improved blood flow detection in the LAD; the success rate in detecting flow of optimal quality was 88% with this approach, whereas it was 11% and 16% with CD in fundamental mode, respectively, before and after contrast. Pulsed wave Doppler results paralleled those of harmonic CD (p < 0.001 contrast harmonic vs. fundamental). In the second group of patients coronary angiography revealed 0% to <40% stenosis in 24 patients (group I), ≥40% to ≤75% in 17 patients (group II) and >75% stenosis in 34 patients (group III). There was a significant difference in CFR among the three groups of patients; CFR for peak diastolic velocity was (mean ± SD): 2.88 ± 0.7 (group I), 2.09 ± 0.5 (group II) and 1.51 ± 0.5 cm/s (group II) (p < 0.05 group I vs. both group II and group III; p < 0.05 group II vs. group III). The whole examination took less than 10 min.CONCLUSIONSContrast-enhanced second harmonic Doppler recording of blood velocity in the LAD is highly feasible and in combination with adenosine it is a rapid, safe and effective method for assessing CFR ratio.

Effect of basal epicardial tone on endothelium-independent coronary flow reserve measurement.

Increased basal epicardial tone may attenuate the coronary flow reserve (CFR) by causing vasodilatation of resistance vessels. We examined the effect of basal epicardial tone on the endothelium-independent CFR measurements in subjects with nonobstructive coronary disease. Patients underwent evaluation of endothelium-independent CFR using adenosine (18-36 microg) and endothelium-dependent CFR using acetylcholine (10(-6) M-10(-4) M), both administered intracoronary. CFR to adenosine, presented as the ratio of Doppler flow velocities post- and pre-adenosine, was measured at baseline and after intracoronary nitroglycerin (200 microg). Nitroglycerin increased the coronary artery diameter by 19.7 +/- 2.5%, and decreased the coronary vascular resistance from 3.0 +/- 0.2 mm Hg/ml/min to 1.8 +/- 0.1 mm Hg/ml/min (p < 0.0001). The response to adenosine at baseline and after nitroglycerin was similar (CFR ratio of 2.52 +/- 0.09 and 2.57 +/- 0.10, respectively, p = NS). The effect of nitroglycerin on the response to adenosine did not correlate with coronary endothelial function (r2 = 0.06, p = 0.13). The basal epicardial tone does not affect CFR measurements in patients with angina and nonobstructive coronary disease.

Adenosine-Induced Coronary Vasodilatation During Transesophageal Doppler Echocardiography

Less invasive methods are replacing traditional invasive means of measuring coronary flow reserve (CFR). Transesophageal echocardiography (TEE) is becoming a useful tool for evaluation of coronary artery disease and has recently been used to measure CFR. This has always been done using dipyridamole, but adenosine has a greater vasodilator potency and more favorable kinetics than dipyridamole. This study was done to evaluate the hypothesis that adenosine is safe, rapid, and accurate in measuring coronary blood flow reserve by TEE Doppler. Forty-nine patients who had recently undergone angiography had a transesophageal echocardiogram with visualization of the coronary arteries and measurement of blood flow velocity in the left anterior descending coronary artery (LAD) during adenosine infusion of 0.14 mg/kg per minute. Angiograms were analyzed by quantitative coronary angiography, and significant stenosis was defined as > 70% lumenal diameter narrowing. Thirty-nine of the 49 patients did not have a significant LAD stenosis (group 1); the remainder had significant disease (group 2). Good spectral Doppler recordings of blood flow velocity in the LAD were obtained in 41 of 46 patients (89%). There were no significant differences in baseline coronary blood flow velocities between the two groups. Hyperemic to baseline flow ratios were significantly higher in patients without significant LAD stenosis for peak (2.83 +/- 1.04 versus 1.78 +/- 0.36) and mean (2.68 +/- 0.96 versus 1.75 +/- 0.39) diastolic velocity. A CFR ratio > 2.1 had a sensitivity of 86%, a specificity of 79%, a positive predictive value of 46%, and a negative predictive value of 96% for the absence of critical LAD stenosis. The infusion was well tolerated. It had to be prematurely terminated in only 3 patients (6.5%), and they were asymptomatic. No patient experienced chest pain, palpitations, or flushing. Intraobserver and interobserver variabilities were low, and reproducibility of data was good (< 4%). Adenosine Doppler TEE is an effective, rapid, safe, and superior means of measuring CFR ratio. This method is convenient for serial measurements of CFR as well as in clinical settings such as evaluation of syndrome X, cardiomyopathy, and aortic regurgitation.

752-6 Visualization of Coronary Arteries and Measurement of Coronary Blood Flow with Transthoracic Echocardiography After Intravenous Administration of a New Echocardlographic Contrast Agent

Imagent ® US (AF0145, Alliance Pharmaceutical Corp.), a new hemodynamically inert perfluorochemical echocardiographic contrast agent, produces excellent left ventricular and blood pool contrast effect after intravenous administration when imaged with conventional (2-D) ultrasound. We evaluated the potential of Contrast Specific Imaging (Acuson) employing second harmonic principles to further enhance the visualization of structures containing contrast agents. Transthoracic images were obtained during injections of 10–40 mg of the agent into the left femoral vein of seven closed chest dogs. Coronary Dopplerflow was simultaneously measured using an intracoronary Doppler wire. No alterations in flow velocities were observed with contrast administration. There was heterogenous opacification of the myocardium following contrast injection: a striking finding was of contrast-enhanced linear, branching structures in the myocardium consistent with coronary vessels. Further exploration of the largest structures (2–3 mm diameter) in the region of the basal ventricular septum was technically possible with pulsed wave Doppler in two dogs. A characteristic coronary Doppler flow pattern was observed (Fig 1a). Transthoracic Doppler flow velocities transiently increased after intracoronary adenosine (Fig 1b). The calculated coronary flow reserve ratio was similar to simultaneous intracoronary Doppler measurements. Intramyocardial coronaryvasculature was observed and coronary flow velocites were measured during transthoracic Contrast Specific Imaging with an intravenously administered contrast agent. These findings suggest that noninvasive assessment of coronary blood flow is possible with echocardiographic contrast enhancement.

Chronically decreased aortic distensibility causes deterioration of coronary perfusion during increased left ventricular contraction

Objectives. This study investigated the long-term effects of decreased aortic distensibility on the heart in relation to coronary perfusion.Background.Aortic distensibility is decreased in patients with atherosclerosis and hypertension and in the elderly. However, the effect of a long-term decrease in aortic distensibility on coronary perfusion has not been fully investigated.Methods. Twelve anesthetized dogs underwent thoracotomy and were allocated to two groups: Group I included six control dogs with a normal aorta; Group II included six dogs with decreased aortic distensibility produced by banding the descending aorta. After 4 to 6 weeks, the dogs had a second operation to measure coronary artery flow and transmural flow distribution. Because the effect of decreased aortic distensibility on coronary perfusion may be affected by ventricular contractility, measurements were performed at baseline and during increased ventricular contraction induced by isoproterenol infusion.Results. At baseline, arterial compliance was reduced by 35% in Group II, but there was no change in total mean arterial resistance. Hemodynamic variables, regional wall motion and coronary flow were also similar in both groups. However, during isoproterenol infusion, coronary flow increased more in Group II than in Group I (p < 0.01), and the coronary flow reserve ratio (maximal peak hyperemic flow divided by rest flow) decreased more in Group II thin in Group I (mean [±SD] 1.9 ± 0.4 vs. 2.4 ± 0.3, p < 0.05). Moreover, although the transmural flow distribution was similar in the two groups at baseline, during isopraterenol infusion the endocardial flow increased less in Group II than in Group I (p < 0.05), and the endocardial/epicardial flow ratio was significantly decreased in Group II compared with Group I (mean [±SD] 0.70 ± 0.18 vs. 0.99 ± 0.22, p < 0.05). The subendocardial electrocardiogram showed ST segment elevation during isoproterenol infusion in Group II (p < 0.05) but not in Group I.Conclusions. These results demonstrate that during increased ventricular contraction, chronically decreased aortic distensibility contributes to a further decrease in the coronary flow reserve ratio, impairs endocardial blood flow and may induce subendocardial ischemia even in the absence of coronary artery stenosis.