Metformin therapy improves coronary microvascular function in patients with polycystic ovary syndrome and insulin resistance

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are thought to have increased cardiovascular risk. Metformin therapy reduces whole-body insulin resistance (IR) in patients with type-2 diabetes mellitus (DM). OBJECTIVE: As insulin resistance accompanying PCOS may be reversed by metformin therapy, we hypothesized that metformin therapy might improve coronary microvascular functions in women with PCOS and IR. PATIENTS AND METHODS: We treated 16 women with PCOS and IR with metformin, and measured coronary flow reserve (CFR) at the beginning and after 6 months of metformin therapy using transthoracic second-harmonic Doppler echocardiography. RESULTS: At the end of the 6 months of metformin therapy, baseline coronary diastolic peak flow velocity (DPFV) did not change significantly (from 24.6 +/- 4.3 to 23.0 +/- 3.1, P = 0.106); however, hyperaemic coronary DPFV (from 68.2 +/- 12.7 to 74.5 +/- 9.7, P = 0.08), and CFR (from 2.75 +/- 0.48 to 3.3 +/- 0.5, P = 0.016) was significantly improved by metformin therapy. CONCLUSION: In women with PCOS, coronary microvascular function and CFR are significantly improved by 6 months of therapy with metformin.     

Altered coronary vasomotor function in young patients with systemic lupus erythematosus

OBJECTIVE: Accelerated atherosclerosis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Altered coronary microvascular function may act as a marker of changes that predispose to the development of significant coronary vascular disease. The purpose of this study was to compare coronary flow reserve (CFR) in a group of premenopausal women with SLE and a group of age-, sex-, and race-matched healthy control subjects. METHODS: Coronary flow velocity in 18 premenopausal women with SLE (mean +/- SD age 29.4 +/- 5.9 years) and 19 matched healthy controls (mean +/- SD age 28.2 +/- 4.3 years) was assessed by transthoracic Doppler echocardiography after an overnight fast. The CFR was calculated as the ratio of hyperemic to baseline coronary blood flow velocity in the left anterior descending coronary artery. Hyperemia was induced by intravenous administration of adenosine triphosphate. RESULTS: The mean +/- SD duration of SLE was 8.2 +/- 7.2 years (range 0.25-25 years), and the mean +/- SD score on the Systemic Lupus Erythematosus Disease Activity Index was 11.0 +/- 5.3 (range 4.0-21.0). Adequate recordings of flow velocity in the left anterior descending artery under both conditions were obtained using an ultrasound procedure in all study subjects. CFR was significantly lower in SLE patients as compared with control subjects (mean +/- SD 3.4 +/- 0.8 versus 4.5 +/- 0.5; P < 0.0001). CONCLUSION: These findings provide evidence that coronary vasomotor function is impaired in patients with SLE and support the notion that many of these young patients have subclinical coronary artery disease.     

Effect of enhanced external counterpulsation on coronary slow flow and its relation with endothelial function and inflammation: a mid-term follow-up study

Background: Although enhanced external counterpulsation (EECP) showed short-term effects in improving coronary flow in patients with coronary slow flow (CSF), whether such improvement is durable remains uncertain, and the relationships between such improvement and changes in endothelial function as well as inflammatory markers have not been elucidated. Objectives: The aim of the present study was to investigate the effects of EECP on transthoracic coronary flow, flow-mediated dilatation (FMD), and high-sensitivity C-reactive protein (hsCRP) in patients with CSF. Methods: Forty-five patients with documented CSF underwent transthoracic Doppler echocardiography (TTDE) for the assessment of coronary diastolic peak flow velocity (DPFV) and coronary flow reserve (CFR), and measurements of FMD and hsCRP; they were then nonrandomly assigned to two groups. Subjects in the control group (n = 24) received only medical therapy, and those in the EECP group (n = 21) were additionally treated with the 36 one-hour sessions of EECP. After 8 weeks of medical/EECP therapy, TTDE, FMD, and hsCRP examinations were repeated, and TTDE was additionally repeated after the 6-month clinical follow-up. Results: In the EECP group, resting DPFV, hyperemic DPFV, and CFR were significantly increased shortly after therapy (p < 0.001) and the improvement was maintained up to the 6-month follow-up, whereas in the control group those variables were not statistically increased. Meanwhile, hsCRP significantly decreased and FMD increased after therapy in the EECP group (p < 0.001). In all subjects, CFR improvement was negatively correlated with hsCRP change and positively correlated with FMD increase (p < 0.001). Conclusions: EECP may have a durable effect in improving coronary flow in patients with CSF. Such improvement is related to the favorable effects of EECP on vascular inflammation and endothelial function.     

Coronary Circulatory Indexes in Non-Infarct-Related Vascular Territories in a Porcine Acute Myocardial Infarction Model

ObjectivesThe aim of this study was to evaluate temporal changes in coronary hemodynamic and physiological indexes in the non-infarct-related artery (IRA), which might be affected by adjacent infarcted myocardium, using an experimental animal model of acute myocardial infarction.BackgroundThere has been debate on the reliability of fractional flow reserve and resting pressure-derived indexes, including instantaneous wave-free ratio, in the non-IRA in patients with acute ST-segment elevation myocardial infarction.MethodsIn Yorkshire swine, acute myocardial infarction was simulated with selective balloon occlusion at the left circumflex coronary artery as the IRA for 30 min. Non-IRA stenosis was created using bare-metal stent implantation in the left anterior descending coronary artery 4 weeks before the experiments. Serial changes in systemic hemodynamic status, coronary pressure, and Doppler-derived coronary flow velocity were measured in a nonoccluded left anterior descending coronary artery as the non-IRA from baseline, balloon occlusion of the left circumflex coronary artery, and 15 min after reperfusion of the left circumflex coronary artery.ResultsAmong the 6 experimental subjects, the median diameter stenosis of the non-IRA was 33.9% (interquartile range: 21.7% to 46.1%). During balloon occlusion of the IRA, there were transient significant changes in both resting and hyperemic aortic pressure, distal coronary pressure, averaged peak velocity, transstenotic pressure gradient, and microvascular resistance of the non-IRA (p < 0.020 for all). After reperfusion of the IRA, the resting averaged peak velocity (p = 0.002) and resting transstenotic pressure gradient (p = 0.004) were significantly increased and resting microvascular resistance (p = 0.004) was significantly decreased compared with their values in the baseline phase. However, the hyperemic averaged peak velocity (p = 0.479), hyperemic transstenotic pressure gradient (p = 0.778), and hyperemic microvascular resistance (p = 0.816) were not significantly different compared with those in the baseline phase. After reperfusion, fractional flow reserve in the non-IRA was not significantly different (0.94 ± 0.01 vs. 0.93 ± 0.01; p = 0.353), while coronary flow reserve (1.93 ± 0.07 vs. 1.36 ± 0.07; p = 0.025) and instantaneous wave-free ratio (0.97 ± 0.01 vs. 0.93 ± 0.01; p = 0.001) were significantly lower than baseline values.ConclusionsIn a porcine model of acute myocardial infarction, occlusion of the IRA induced significant changes in systemic hemodynamic status and coronary circulatory indexes of the non-IRA. However, after reperfusion of the IRA, fractional flow reserve did not change significantly, whereas coronary flow reserve and instantaneous wave-free ratio showed significant changes compared with baseline values.     

Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions

BACKGROUND: Fractional flow reserve (FFR) and coronary blood flow velocity reserve (CFR) represent physiological quantities used to evaluate coronary lesion severity and to make clinical decisions. A comparison between the outcomes of both diagnostic techniques has not been performed in a large cohort of patients with intermediate coronary lesions. METHODS AND RESULTS: FFR and CFR were assessed in 126 consecutive patients with 150 intermediate coronary lesions (between 40% and 70% diameter stenosis by visual assessment). Agreement between outcomes of FFR and CFR, categorized at cut-off values of 0.75 and 2.0, respectively, was observed in 109 coronary lesions (73%), whereas discordant outcomes were present in 41 lesions (27%). In 26 of these 41 lesions, FFR was <0.75 and CFR>or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). 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, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034). CONCLUSIONS: Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement.     

Impaired coronary microvascular and left ventricular diastolic functions in patients with ankylosing spondylitis

BackgroundIt has been shown that the patients with inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis have an increased risk of developing atherosclerosis. However, the association of ankylosing spondylitis (AS) to atherosclerosis and related diseases is still controversial. Accordingly, we investigated coronary flow reserve (CFR) and left ventricular (LV) diastolic function in patients with AS using transthoracic Doppler echocardiography.MethodsCFR and LV diastolic function were studied in 40 patients with AS (38.9 ± 10.2 years, 26 males) and 35 healthy volunteers (37.5 ± 6.4 years, 23 males). Coronary diastolic peak flow velocities (DPFV) were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline DPFV. LV diastolic function was assessed by both standard and tissue Doppler imaging.ResultsDemographic features and coronary risk factors except diastolic blood pressure were similar between the groups. CFR were significantly lower in the AS group than in the control group (2.20 ± 0.46 versus 3.02 ± 1.50, P < 0.0001). Reflecting LV diastolic function mitral A-wave and E/A ratio were borderline significant, and mitral E-wave deceleration time and isovolumic relaxation time were significantly different between the groups. Serum hsCRP and TNF-α levels were significantly higher in the patients with AS, and hsCRP and TNF-α levels independently correlated with CFR.ConclusionThese findings show that CFR reflecting coronary microvascular function and LV diastolic function are impaired in patients with AS, and severity of these impairments correlate well with hsCRP and TNF-α. These results suggest that impaired CFR may be an early manifestation of cardiac involvement in patients with AS.     

Endothelial-mediated coronary flow reserve and its relation to mitral annular tissue Doppler velocities in offspring of hypertensive parents

Background: Although coronary flow reserve (CFR) is reduced in hypertensive patients, data regarding the endothelial response of coronary vasomotion and its relation to left ventricular (LV) function in their offspring is limited. Objective: To investigate the endothelial response of coronary flow, using cold pressor test (CPT), in offspring of hypertensive parents and its impact on LV diastolic function. Subjects and Methods: The study population consisted of 32 healthy young offspring (mean age 23.5 ± 7.1 years) of hypertensive parents and 26 aged matched volunteers (healthy offspring of normotensive parents) as controls. Coronary blood flow velocities were recorded in all subjects at rest and after CPT; a stimulus that can be considered totally endothelium‐dependent. CFR was calculated as the ratio of hyperemic‐to‐resting diastolic peak velocities. Doppler echocardiographic assessment was performed using both conventional and tissue Doppler assessment. Results: Coronary diastolic peak velocities at rest was comparable between the two groups (27.1 ± 6.2 vs 26.4 ± 5.8; P > 0.05); but the velocities were significantly lower after CPT in offspring of hypertensive parents (P < 0.02), with highly significant lower CFR (P < 0.0001). Conventional echo‐Doppler variables were comparable in both groups, whereas tissue Doppler assessment demonstrated significant LV diastolic dysfunction among offspring of hypertensive parents. The CPT‐CFR was significantly correlated to tissue Doppler diastolic dysfunction in this group (For Em, Am and Em/Am, r was 0.65, 0.59 and 0.61, respectively, and P < 0.001). Conclusion: Offspring of hypertensive parents have coronary endothelial dysfunction that appears in response to physiological stimuli (CPT). The coronary endothelial dysfunction is associated with latent LV diastolic dysfunction. (Echocardiography 2011;28:1113‐1118)     

Microvascular Resistance Reserve to Assess Microvascular Dysfunction in ANOCA Patients

BackgroundMicrovascular resistance reserve (MRR) is a new index to assess coronary microvascular (dys)function, which can be easily measured invasively using continuous thermodilution. In contrast to coronary flow reserve (CFR), MRR is independent of epicardial coronary disease and hemodynamic variations. Its measurement is accurate, reproducible, and operator independent.ObjectivesThe aim of this study was to establish the range of normal values for MRR and to determine an optimal cutoff point.MethodsIn this exploratory study in 214 patients with angina and no obstructive coronary artery disease, after excluding significant epicardial disease, all physiological parameters, such as fractional flow reserve, index of microvascular resistance, CFR, absolute blood flow, absolute microvascular resistance, and MRR, were measured. On the basis of concordant positive or concordant negative results of index of microvascular resistance and CFR, subgroups of patients were defined with high probability of either normal (n = 122) or abnormal (n = 24) microcirculatory function, and MRR was studied in these groups.ResultsMean MRR in the “normal” group was 3.4 compared with a mean MRR of 1.9 in the “abnormal” group; these values were significantly different between the groups. MRR >2.7 ruled out coronary microvascular dysfunction (CMD) with a certainty of 96%, whereas MRR <2.1 indicated the presence of CMD with a similar high certainty of 96%.ConclusionsMRR is a suitable index to distinguish the presence or absence of CMD in patients with angina and no obstructive coronary artery disease. The present data indicate that an MRR of 2.7 virtually excludes the presence of CMD, while an MRR value <2.1 confirms its presence.     

Estimation of myocardial hemodynamics before and after intervention in children with Kawasaki disease

OBJECTIVES: We used myocardial fractional flow reserve (FFR(myo)) and coronary flow reserve (CFR) to estimate cut-off values for assessment of the functional severity of coronary stenosis and myocardial ischemia, and we tested the usefulness of coronary blood hemodynamic measurements before and after plain old balloon angioplasty (POBA) and coronary artery bypass graft surgery (CABG). BACKGROUND: Fractional flow reserve and CFR are useful for assessing the functional severity of coronary artery stenosis, coronary microvascular dysfunction, and myocardial ischemia during cardiac catheterization in adults. However, there have been no reports on the use of these measurements in children with Kawasaki disease (KD). METHODS: The study group included 128 patients with 314 coronary branches. The subjects were classified into three groups: normal coronary group, with 206 branches; abnormal coronary artery without ischemia group, with 58 branches; and ischemia group, with 50 branches. RESULTS: In each branch, CFR and FFR(myo) were significantly lower in the ischemia group than in the other groups. Cut-off values for assessing the functional severity of coronary stenosis and CFR were approximately equal to those obtained for adults (CFR: <2.0; FFR(myo): <0.75). We obtained very high sensitivity and specificity for estimating myocardial ischemia using CFR and FFR(myo) (CFR: 94.0% and 98.5%, respectively; FFR(myo): 95.7% and 99.1%, respectively). Both CFR and FFR(myo) were reliable indicators of coronary hemodynamics before and after POBA and CABG. CONCLUSIONS: Together, CFR and FFR(myo) provide a useful index for assessing the functional severity of coronary artery stenosis and myocardial ischemia and estimating the effectiveness of POBA and CABG in children with KD, the same as they do for adults.     

Heterogeneity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: implications for clinical practice

Background Women with chest pain in the absence of obstructive coronary artery disease (CAD) frequently have coronary microvascular dysfunction and inducible myocardial ischemia. Microvascular dysfunction is commonly diagnosed by demonstrating abnormal flow reserve in a single coronary artery during angiography. Therefore, diagnostic accuracy is dependent on homogeneity of microvascular dysfunction in the myocardium. Methods In the Women's Ischemia Syndrome Evaluation (WISE), 34 women with chest pain and no significant CAD and 9 female control subjects underwent ¹³N-NH₃ positron emission tomography to measure adenosine-induced changes in myocardial perfusion (ie, coronary flow reserve [CFR]). Flow reserve was correlated among the left anterior descending (LAD), circumflex (LCx), and right (RCA) coronary artery distributions. Results The mean CFR in the LAD, LCx, and RCA was 2.85 ± 1.35, 2.58 ± 0.94, and 3.24 ± 1.42, respectively. Concordance in the classification of microvascular function as normal (CFR ≥2.5) versus abnormal was present in the LAD and RCA, LAD and LCx, and RCA and LCx distributions in only 71.8%, 66.7%, and 61.6% of patients, respectively. There was a modest degree of correlation of CFR between the LAD and RCA (r = 0.79, P < .001), LAD and LCx (r = 0.61, P < .001), and LCx and RCA (r = 0.57, P < .001). Comparison of CFR in the 3 coronary arteries simultaneously in all patients demonstrated that the LCx had values that were significantly lower than the RCA and LAD distributions. Conclusion Substantial discordance of classification of microvascular function among coronary artery distributions in women with chest pain and no CAD suggests that microvascular dysfunction is distributed heterogeneously in the myocardium. Assessment of CFR in a single coronary artery during cardiac catheterization may not provide an accurate assessment of the coronary microcirculation in women with chest pain not attributable to CAD. (Am Heart J 2003;145:628-35.)     

Altered coronary flow properties in diffuse coronary artery ectasia

Objectives The purpose of this study was to investigate coronary blood flow properties in patients with diffuse coronary artery ectasia (CAE) associated with exercise-induced myocardial ischemia.Methods Seventeen patients with diffuse CAE and without coexisting coronary artery stenosis were enrolled in the study (CAE group). CAE was defined as luminal dilatation 1.5 to 2 times that of the adjacent normal coronary artery segment or the diameter of the corresponding coronary artery of the control group when there was no normal segment. The age- and sex-matched control group (n = 20) comprised patients with normal epicardial coronary arteries. Coronary blood flow velocities were obtained invasively by use of Doppler scanning flow wire. Coronary flow reserve (CFR) was measured by administration of intracoronary papaverine as the hyperemic stimulus. Volumetric coronary blood flow was estimated by multiplying the velocity time integral of coronary blood flow with the cross-sectional area of the coronary artery and the heart rate.Results Fifteen patients with CAE, but none of the patients in the control group, had electrocardiographic signs of myocardial ischemia at peak exercise on ergometry. Baseline average peak velocities (APVs) of coronary blood flow were similar in the 2 groups. Peak hyperemic APVs of coronary blood flow were lower in the CAE group than in the control group (17.5 ± 7.4 cm/s vs 41.5 ± 12.6 cm/s, respectively, P < .001). Volumetric coronary blood flow was significantly higher in the CAE group than in the control group, both at rest and at hyperemia (146.3 ± 71.2 cm³/min vs 45.1 ± 16.1 cm³/min, respectively, P < .001, and 202 ± 87.3 cm³/min vs 104.1 ± 37.6 cm³/min, respectively, P < .003). The mean CFR of the CAE group was significantly reduced compared with that of the control group (1.51 ± 0.31 vs 2.67 ± 0.52, respectively, P < .001).Conclusions The CFR is significantly reduced in patients with diffuse CAE compared to a matched control group. Although volumetric coronary blood flow is significantly higher in CAE, microcirculatory dysfunction that is reflected as depressed CFR may be the underlying cause of exercise-induced myocardial ischemia. (Am Heart J 2003;145:66-72.)     

经皮冠状动脉内多普勒超声技术对冠状动脉血液动力学的研究

目的 :评价冠状动脉 (冠脉 )内多普勒血流钢丝测量冠脉血流速度和血流储备 (CFR)的应用价值。　　方法 :在 2 1例冠脉狭窄患者 (冠脉狭窄组 )和 12例正常冠脉者 (对照组 )中 ,利用冠脉内多普勒血流钢丝和冠脉内注射罂粟碱测量了冠脉的血流速度和 CFR。　　结果 :左前降支冠脉狭窄远端的平均最大血流速度、舒张期最大血流速度、舒张期与收缩期流速比值和 CFR均显著低于对照组测值。　　结论 :应用冠脉内多普勒超声技术可准确测量正常和冠脉狭窄患者的冠脉血流速度和 CFR,冠脉内注射罂粟碱安全、可靠 ,这一方法的临床应用对冠心病患者冠脉血液动力学的评价提供了可靠的方法。     

Coronary flow reserve is impaired in subclinical hypothyroidism

OBJECTIVE: Although the cardiovascular system is highly sensitive to thyroid hormones, the cardiovascular effects of subtle thyroid dysfunction such as subclinical hypothyroidism (SHT) remain unclear. Therefore, we investigated coronary flow reserve (CFR) reflecting coronary microvascular function in patients with SHT. METHODS: Fifty subjects with SHT and 30 control subjects with normal serum thyroid hormones and TSH levels were included in this study. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocity. RESULTS: Age, gender, diastolic and systolic blood pressure, body mass index (BMI), serum lipid parameters, and thyroid hormone levels were similar between the groups. Heart rate was significantly lower in the SHT group. Left ventricular diastolic filling parameters were significantly different in the SHT group while other echocardiographic parameters were similar. CFR values were significantly lower in subjects with SHT than in the control group (2.38 +/- 0.44 vs. 2.98 +/- 0.47, p < 0.0001). CONCLUSIONS: These findings suggest that CFR, which reflects coronary microvascular function, is impaired in patients with SHT.     

Effects of atorvastatin on coronary flow reserve in patients with slow coronary flow

BACKGROUND: Statins improve endothelial functioning in patients with coronary artery disease and hypercholesterolemia, while substantially little is known about induced changes in myocardial microcirculation. However, although previous studies have suggested that microvascular abnormalities and endothelial dysfunction is responsible for slow coronary flow (SCF), there is no study investigating possible effects of statins on coronary microvascular function in patients with SCF. HYPOTHESIS: We prospectively investigated the effects of short-term lipid-lowering therapy with atorvastatin on coronary flow reserve (CFR) reflecting coronary microvascular function in patients with SCF assessed by transthoracic Doppler echocardiography (TTDE). METHODS: In an open clinical trial, CFR was studied in 20 subjects with SCF. TTDE was used to assess CFR at baseline as well as after 8 weeks of atorvastatin therapy. Coronary flow was quantified according to TIMI frame count (TFC). Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. RESULTS: CFR was independently correlated with TFC. After 8 weeks of atorvastatin therapy, CFR values increased significantly (1.95 +/- 0.38 vs. 2.54 +/- 0.56, (p < 0.001). No change in hemodynamic parameters was noted during the entire study. The improvement in CFR was not correlated to the amount of lipid-lowering effect of atorvastatin. CONCLUSIONS: These findings suggest that short-term lipid-lowering therapy with atorvastatin improved CFR, which reflects coronary microvascular functioning in patients with SCF.     

Noninvasive evaluation of flow reserve in the left anterior descending coronary artery in patients with cardiac syndrome X

Data on coronary flow reserve (CFR) in patients with syndrome X are still controversial. Further, noninvasive evaluation of epicardial and microvascular flow reserves in these patients has never been performed. In 17 patients with syndrome X and in 17 age- and gender-matched control subjects, CFR in the mid left anterior descending coronary artery (LAD) was evaluated by transthoracic color and pulse-wave Doppler using a 7-mHz probe (Sequoia, Siemens). Peak diastolic LAD flow was calculated at rest and at peak adenosine (140 microg/kg/min intravenously in 90 seconds). Myocardial contrast echocardiography (MCE) was performed at rest and during adenosine use by real-time cadence pulse sequencing and intravenous SonoVue (Bracco; 5 ml at 1 ml/min) and microvascular blood volume (A), velocity (beta), and flow (Axbeta) by replenishing curves (y = A[1 - e(betat)]). CFR was measured by Doppler echocardiography as an adenosine/rest velocity ratio and by MCE as a microvascular volume, velocity, and flow adenosine/rest ratio. Compared with controls, patients with syndrome X demonstrated lower LAD CFR and velocity and flow microvascular flow reserves (p <0.01, <0.005, and <0.005, respectively). In patients with syndrome X, those with angina and ST-segment depression during adenosine testing had even lower LAD CFR and velocity and flow microvascular flow reserves compared with those with no symptoms (p <0.0001, <0.0001, and <0.005, respectively). LAD CFR demonstrated a significant linear correlation with velocity microvascular flow reserve (r = 0.92, p <0.0001) and flow microvascular flow reserve (r = 0.77, p <0.0001). In conclusion, CFR in the LAD, successfully evaluated by transthoracic Doppler echocardiography and MCE, is significantly decreased in patients with syndrome X and even more in those with angina pectoris and ST-segment depression during adenosine testing. Thus, noninvasive evaluation of CFR by echocardiography is feasible and provides information on the severity of microvascular impairment.     

Subendocardial viability ratio as an index of impaired coronary flow reserve in hypertensives without significant coronary artery stenoses

Subendocardial viability ratio (SEVR), calculated through pulse wave analysis, is an index of myocardial oxygen supply and demand. Our aim was to evaluate the relationship between coronary flow reserve (CFR) and SEVR in 36 consecutive untreated hypertensives (aged 57.9 years, 12 males, all Caucasian) with indications of myocardial ischaemia and normal coronary arteries in coronary angiography. CFR was calculated by a 0.014-inch Doppler guidewire (Flowire, Volcano, San Diego, CA, USA) in response to bolus intracoronary administration of adenosine (30-60?μg). SEVR was calculated by radial applanation tonometry, while diastolic function was evaluated by means of transmitral flow and tissue Doppler imaging. Hypertensive patients with low CFR (n=24) compared with those with normal CFR (n=12) exhibited significantly decreased SEVR by 24.5% (P=0.002). In hypertensives with low CFR, CFR was correlated with SEVR (r=0.651, P=0.001). After applying multivariate linear regression analysis, age, left ventricular mass index, Em/Am, 24-h diastolic blood pressure (BP) and SEVR turned out to be the only independent predictors of CFR (adjusted R(2)=0.718). Estimation of SEVR by using applanation tonometry may provide a reliable tool for the assessment of coronary microcirculation in essential hypertensives with indications of myocardial ischaemia and normal coronary arteries.     

Effect of Sex Difference of Coronary Microvascular Dysfunction on Long-Term Outcomes in Deferred Lesions

ObjectivesThis study investigated the sex difference of long-term cardiovascular outcomes on coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with deferred coronary artery lesions.BackgroundCoronary microvascular dysfunction is associated with poorer long-term outcomes. It can be assessed by CFR and the IMR.MethodsThe study prospectively enrolled 434 patients (133 women and 301 men) and analyzed CFR, IMR, fractional flow reserve, and quantitative coronary angiography. Clinical outcomes were assessed by major adverse cardiovascular event(s) (MACE) of cardiac death, myocardial infarction, and revascularization during 5 years of follow-up. The study protocol was approved by the Institutional Review Board or Ethics Committee at each participating center, and all patients provided written informed consent. The study protocol was in accordance with the Declaration of Helsinki.ResultsWomen had milder epicardial disease compared with men (fractional flow reserve: 0.91 [interquartile range (IQR): 0.87 to 0.96] vs. 0.90 [IQR: 0.86 to 0.95]; p = 0.037). IMR was similar between the sexes, but CFR was lower in women (2.69 [IQR: 2.08 to 3.90] vs. 3.20 [IQR: 2.20 to 4.31]; p = 0.006) due to a shorter resting mean transit time, whereas hyperemic mean transit times were similar. At 5-year follow-up, MACE was significantly lower in women compared with men (1.1% vs. 5.5%; p = 0.017). Sex, diabetes mellitus, and CFR were independent predictors for MACE for all patients. The risk of MACE was significantly higher in men with low versus high CFR (hazard ratio: 4.58; 95% confidence interval: 1.85 to 11.30; p = 0.011) which was not seen in women.ConclusionsThere was no sex difference in microvascular function by IMR. CFR was lower in women due to a higher resting coronary flow; however, long-term clinical outcomes in deferred lesions were better in women compared with men. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093).     

Measurement of coronary flow reserve and its role in patient care

Coronary anatomy and myocardial blood flow are major determinants of clinical symptomatology and survival in patients with coronary artery disease. While coronary anatomy has been successfully assessed by coronary angiography and intravascular ultrasound imaging, measurements of coronary blood flow are more difficult and their prognostic value has not been definitively evaluated. Measurements of coronary flow reserve (CFR), defined as maximal hyperemic flow divided by resting flow, have been used to assess the functional significance of coronary artery lesions. However, functional assessment of epicardial coronary lesions is limited by several factors, such as diffuse coronary artery disease, small-vessel disease, regional variations in myocardial flow, endothelial dysfunction, and left ventricular hypertrophy. CFR can be measured by several techniques, each one with distinct advantages and limitations, which are discussed in this review. An important distinction is between techniques that measure coronary blood flow (e.g., positron emission tomography) and those that measure blood flow velocity (e.g., Doppler catheters), from which coronary velocity reserve (CVR) is calculated. Although clinical CFR measurements have been possible for over fifteen years, their implementation in patient care has been slow due to several factors including the requirement for a sophisticated technology, the difficult interpretation of CFR results, and the limited knowledge of their prognostic value. While a normal CFR in patients with single vessel coronary disease is associated with a good prognosis, the converse has not been established, i.e., that there is a critical reduction in CFR that requires interventional treatment. A recent study (DEBATE) showed a decrease in the incidence of cardiac events at 6 months after coronary balloon angioplasty in patients with a post-procedural percent diameter stenosis <35% and CVR >2.5. The complex relation between coronary anatomy, myocardial perfusion, and patient outcome have enormous implications for both patient care and health costs, which need to be addressed in future prospective trials. Received: 20 October 1997, Returned for revision: 9 December 1997, Revision received: 9 April 1998, Accepted: 23 April 1998     

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

Background and aimAbnormal 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 resultsTwenty-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.ConclusionCoronary 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.     

Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease

ObjectivesThis study assessed the prevalence of coronary microvascular abnormalities in patients presenting with chest pain and nonobstructive coronary artery disease (CAD).BackgroundCoronary microvascular abnormalities mediate ischemia and can lead to an increased risk of cardiovascular events.MethodsUsing an intracoronary Doppler guidewire, endothelial-dependent microvascular function was examined by evaluating changes in coronary blood flow in response to acetylcholine, whereas endothelial-independent microvascular function was examined by evaluating changes in coronary flow velocity reserve in response to intracoronary adenosine. Patients were divided into 4 groups depending on whether they had a normal (+) or abnormal (−) coronary blood flow (CBF) in response to acetylcholine (Ach) and a normal (+) or abnormal (−) coronary flow velocity reserve (CFR) in response to adenosine (Adn): CBFAch+, CFRAdn+ (n = 520); CBFAch−, CFRAdn+ (n = 478); CBFAch+, CFRAdn− (n = 173); and CBFAch−, CFRAdn− (n = 268).ResultsTwo-thirds of all patients had some sort of microvascular dysfunction. Women were more prevalent in each group (56% to 82%). Diabetes was uncommon in all groups (7% to 12%), whereas hypertension and hyperlipidemia were relatively more prevalent in each group, although rates for most conventional cardiovascular risk factors did not differ significantly between groups. There were no significant differences in the findings of noninvasive functional testing between groups. In a multivariable analysis, age was the only variable that independently predicted abnormal microvascular function.ConclusionsPatients with chest pain and nonobstructive CAD have a high prevalence of coronary microvascular abnormalities. These abnormalities correlate poorly with conventional cardiovascular risk factors and are dissociated from the findings of noninvasive functional testing.