Coronary Microvascular Function In Patients Research Articles

Rapid Fire Abstract session: multimodality imaging of ischaemic heart disease928Regional left ventricular longitudinal function and myocardial blood flow929The influence of plaque burden, morphology and inflammatory markers on coronary microvascular function in patients with chest pain and unobstructed coronary arteries930Predictors of coronary microcirculatory function after primary percutaneous coronary intervention in STEMI patients932Prediction of adverse events after ST segment-elevation myocardial infarction by

Rapid Fire Abstract session: multimodality imaging of ischaemic heart disease928Regional left ventricular longitudinal function and myocardial blood flow929The influence of plaque burden, morphology and inflammatory markers on coronary microvascular function in patients with chest pain and unobstructed coronary arteries930Predictors of coronary microcirculatory function after primary percutaneous coronary intervention in STEMI patients932Prediction of adverse events after ST segment-elevation myocardial infarction by

Effects of prasugrel versus clopidogrel on coronary microvascular function in patients undergoing elective percutaneous coronary intervention: A randomized double-blind study

Effects of prasugrel versus clopidogrel on coronary microvascular function in patients undergoing elective percutaneous coronary intervention: A randomized double-blind study

Prognostic significance of coronary sinus filling time in patients with angina and normal coronaries at one year follow up

BackgroundCoronary sinus filling time (CSFT) has been proposed as a simple method for assessment of coronary microvascular function in patients with angina and normal coronaries. But its correlation with inducible ischemia and prognostic significance in predicting future cardiovascular events has not been studied. The present study assessed the prognostic significance of CSFT during one year of follow up. MethodsWe compared coronary sinus filling time of patients with angina and normal coronaries with that of control population. Control group was formed by those patients with supraventricular arrhythmia undergoing radiofrequency ablation and having normal coronaries. Baseline treadmill test (TMT) parameters like workload, duration and Duke Score were assessed. Patients were followed up for one year and a composite of cardiovascular mortality and non-fatal myocardial infarction was analyzed. Number of patients presenting to emergency or outpatient department with recurrent chest pain symptoms during one year follow up was considered for secondary outcome analysis. Coronary sinus filling time was analyzed with respect to cardiovascular events, repeat hospitalization for recurrent angina and TMT parameters. ResultsTotal 72 patients and 16 controls were studied. Mean CSFT value in the study group was 5.31 ± 1.03 sec and in the control group was 4.16 ± 0.72 sec and the difference was significant (p value = 0.0001). No correlation was found between baseline and repeat TMT parameters with CSFT. There was no cardiovascular mortality or hospitalization for non-fatal MI during one year follow up. But patients with frequent emergency or outpatient department visits with chest pain had a high CSFT compared with asymptomatic patients (p value = 0.005). ConclusionCoronary sinus filling time may be used as a simple marker of microvascular dysfunction in patients with angina and normal coronaries. Patients with recurrent chest pain symptoms after one year follow up were found to have high CSFT compared to asymptomatic patients.

Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes - a randomized, single-blinded, cross-over pilot study.

BackgroundImpaired coronary microcirculation is associated with a poor prognosis in patients with type 2 diabetes. In the absence of stenosis of major coronary arteries, coronary flow reserve (CFR) reflects coronary microcirculation. Studies have shown beneficial effects of glucagon-like peptide-1 (GLP-1) on the cardiovascular system. The aim of the study was to explore the short-term effect of GLP-1 treatment on coronary microcirculation estimated by CFR in patients with type 2 diabetes.MethodsPatients with type 2 diabetes and no history of coronary artery disease were treated with either the GLP-1 analogue liraglutide or received no treatment for 10 weeks, in a randomized, single-blinded, cross-over setup with a 2 weeks wash-out period. The effect of liraglutide on coronary microcirculation was evaluated using non-invasive trans-thoracic Doppler-flow echocardiography during dipyridamole induced stress. Peripheral microvascular endothelial function was assessed by Endo-PAT2000®. Interventions were compared by two-sample t-test after ensuring no carry over effect.ResultsA total of 24 patients were included. Twenty patients completed the study (15 male; mean age 57 ± 9; mean BMI 33.1 ± 4.4, mean baseline CFR 2.35 ± 0.45). There was a small increase in CFR following liraglutide treatment (change 0.18, CI95% [-0.01; 0.36], p = 0.06) but no difference in effect in comparison with no treatment (difference between treatment allocation 0.16, CI95% [-0.08; 0.40], p = 0.18). Liraglutide significantly reduced glycated haemoglobin (HbA1c) (-10.1 mmol/mol CI95% [-13.9; -6.4], p = 0.01), systolic blood pressure (-10 mmHg CI95% [-17; -3], p = 0.01) and weight (-1.9 kg CI95% [-3.6; -0.2], p = 0.03) compared to no treatment. There was no effect on peripheral microvascular endothelial function after either intervention.ConclusionsIn this short-term treatment study, 10 weeks of liraglutide treatment had no significant effect on neither coronary nor peripheral microvascular function in patients with type 2 diabetes. Further long-term studies, preferably in patients with more impaired microvascular function and using a higher dosage of GLP-1 analogues, are needed to confirm these findings.Trial registrationClinicalTrials.gov: NCT01931982.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0206-3) contains supplementary material, which is available to authorized users.

Thermodilutional Confirmation of Coronary Microvascular Dysfunction in Patients With Recurrent Angina After Successful Percutaneous Coronary Intervention

BackgroundRecurrent angina (RA) after percutaneous coronary intervention (PCI) remains a challenging problem that confronts cardiologists in routine clinical practice. In patients without epicardial coronary causes, RA is commonly speculated as resulting from coronary microvascular dysfunction. The aim of this study was to investigate the coronary microvascular function in patients with RA late after successful PCI and without epicardial stenosis at the time of repeat angiography. MethodsWe studied 39 consecutive patients with RA in whom PCI was successfully performed 6 to 12 months previously because of angina and single-vessel disease and without restenosis and disease progression at the time of repeat angiography. Twelve subjects without RA were recruited as the control group. Thermodilution-derived coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured using a pressure-temperature sensor-tipped coronary wire. The exercise treadmill test was performed according to the Bruce protocol. ResultsPatients with RA showed significantly higher IMR and lower CFR than control subjects, in the target arteries and in the reference vessels (P < 0.05). The hyperemic IMR was more remarkably increased in the target arteries than in the reference vessels (29.3 ± 11.7 vs 24.4 ± 9.7; P = 0.008). The hyperemic IMR was increased and the CFR was impaired more significantly in patients with a positive exercise treadmill test (P < 0.05). ConclusionsUsing an intracoronary thermodilution method, to our knowledge, we have for the first time confirmed that, in patients who underwent successful coronary stenting and without epicardial stenosis at repeat angiography late after PCI, coronary microvascular dysfunction was responsible for the RA.

Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease

Background: Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker released from leukocytes and endothelial cells that has been associated with atherosclerotic cardiovascular disease. We hypothesized that plasma suPAR level is an independent predictor of coronary microvascular function. Methods: Coronary blood flow velocity and plasma suPAR levels were evaluated in patients with non-obstructive coronary artery disease. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal average peak blood flow velocity and coronary microvascular dysfunction was defined as CFR ≤ 2.0 in the setting of a fractional flow reserve value of ≥0.75. Plasma suPAR levels were measured using ELISA technique. The association between suPAR and CFR was investigated using univariate and multivariate regression analyses. Results: In 66 patients, 47% were men, 26% had diabetes, 68% had hypertension and 76% had dyslipidemia. Mean age was 55 ± 12 years and median suPAR level 2.82 (2.08–3.40) ng/mL. Plasma suPAR levels correlated with age (r = 0.31, p = 0.01), body mass index (r = 0.25, p = 0.04) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.33, p = 0.009). While median suPAR level was not significantly different in patients with different cardiovascular risk factors, patients on statin therapy had significantly higher suPAR level (p = 0.03). SuPAR correlated negatively with CFR and, after multivariate adjustment for established cardiovascular risk factors, medications profiles and hs-CRP, suPAR remained an independent predictor of CFR (B = −0.30, p = 0.04), indicating an independent association between suPAR level and coronary microvascular function. Conclusions: In this cross-sectional study, plasma suPAR level was an independent predictor of coronary microvascular function. Larger prospective clinical trials are warranted to investigate the prognostic value of this novel biomarker and the role of immune dysregulation in coronary microvascular disease.

Abstract 12019: Differential Effect of Ticagrelor versus Clopidogrel on Coronary Microvascular Function in Patients With Coronary Aertery Disease

Introduction: Differential Effect of Ticagrelor Versus Clopidogrel on Coronary Microvascular Function in Patients with Coronary Aertery Disease Background and Objectives: Ticagrelor is a new antiplatelet drug directly blocking P2Y12-adenosine diphosphate (ADP) receptors, which show a better clinical profile compared to clopidogrel in patients with acute coronary syndrome. Ticagrelor inhibits adenosine reuptake and increases coronary blood flow by a direct dilation of the microcirculation. We aimed to evaluate the effect of ticagrelor on coronary mircrovascular function in patient with coronary artery disease (CAD) in comparison with clopidogrel. Subjects and Methods: Twenty four patient with CAD were randomized to receive a single dose of ticagrelor (180 mg) or clopidogrel (300mg or on treatment state). Coronary microvascular function was invasively measured by using the index of microvascular resistance (IMR) and coronary flow reserve (CFR). The IMR was calculated from the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit time (hTmn). The CFR was calculated dividing the hTmn by baseline mean transit time. Results: There were no significant differences in baseline clinical and angiographic characteristics.CFR was not significantly different in both groups. (median: 4.00 [interquartile range(IQR) 2.30 to 4.92] vs 5.10 [IQR: 3.72 to 7.90], p = 0.24) However, IMR was significantly lower in ticagrelor than clopidogrel treated patients at 140 μg/kg per minute adenosine infusion rate. (median: 10.74 [interquartile range (IQR) 8.02 to 12.31] vs 15.56 [IQR: 10.77 to 29.74], p =0.05). Conclusions: In patients with CAD, ticagrelor might improves coronary microvascular functionel. These results suggest that ticagrelor could contribute to better clinical outcomes in CAD patients.

Increased morning blood pressure surge and coronary microvascular dysfunction in patient with early stage hypertension

Morning blood pressure surge (MBPS) is defined as an excessive increase in blood pressure (BP) in the morning from the lowest systolic BP during sleep, and it has been reported as a risk factor for cardiovascular events in current clinical studies. In this study, we evaluated the association between the rate of BP variation derived from ambulatory BP monitoring data analysis and coronary microvascular function in patients with early stage hypertension. One hundred seventy patients with prehypertension and Stage 1 hypertension who fulfilled the inclusion and exclusion criteria were included in the study. We divided our study population into two subgroups according to the median value of coronary flow reserve (CFR). Patients with CFR values <2.5 were defined as the impaired CFR group, and patients with CFR values ≥2.5 were defined as the preserved CFR group, and we compared the MBPS measurements of these two subgroups. CFR was measured using transthoracic Doppler echocardiography (TTDE). Ambulatory 24-hour systolic and diastolic BP, uric acid, systolic MBPS amplitude, diastolic MBPS amplitude, high-sensitivity C-reactive protein, and mitral flow E/A ratio were statistically significant. These predictors were included in age- and gender-adjusted multivariate analysis; ambulatory 24-hour systolic BP (ß = 0.077, P < .001; odds ratio [OR] = 1.080; 95% confidence interval [CI] [1.037–1.124]) and systolic MBPS amplitude (ß = 0.043, P = .022; OR = 1.044; 95% CI [1.006–1.084]) were determined to be independent predictors of impaired CFR (Hosmer–Lemeshow test, P = .165, Nagelkerke’s R2 = 0.320). We found that increased changes in MBPS values in patients with prehypertension and Stage 1 hypertension seemed to cause microvascular dysfunction in the absence of obstructive coronary artery disease.

Peripheral Arterial Function and Coronary Microvascular Function in Patients with Variant Angina

Objectives: In this study, we assessed whether any abnormalities in coronary microvascular and peripheral vasodilator functions are present in patients with variant angina (VA) caused by epicardial coronary artery spasm (CAS). Methods: We studied 23 patients with VA (i.e. angina at rest, ST-segment elevation during angina attacks and documented occlusive CAS at angiography) and 18 matched healthy controls. Endothelium-dependent and -independent coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to adenosine and the cold pressor test (CPT) in the left anterior descending artery by transthoracic Doppler echocardiography. Systemic endothelium-dependent and -independent arterial dilator function was assessed by measuring brachial flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), respectively. Results: In VA patients, CBF responses to both adenosine (1.71 ± 0.25 vs. 2.97 ± 0.80, p < 0.01) and CPT (1.68 ± 0.23 vs. 2.58 ± 0.60, p < 0.01) were reduced compared to controls. Brachial FMD was also lower (3.87 ± 2.06 vs. 8.51 ± 2.95%, p < 0.01), but NMD was higher (16.7 ± 1.8 vs. 11.9 ± 1.4%, p < 0.01) in patients compared to controls. Differences were independent of the presence of coronary atherosclerotic lesions at angiography. Conclusions: Our data show that patients with VA have a generalized vascular dysfunction that involves both peripheral artery vessels and coronary microcirculation.

Relation of Albuminuria to Coronary Microvascular Function in Patients With Chronic Kidney Disease

The relation between albuminuria and coronary microvascular function in patients with chronic kidney disease (CKD) has not been fully investigated. Therefore, we sought to assess whether albuminuria is associated with coronary flow velocity reserve (CFVR) impairment in patients with CKD. Coronary flow study was prospectively performed in 175 patients with CKD. CFVR of the left anterior descending artery was measured to evaluate coronary microvascular function using transthoracic echocardiography. We divided the patients into 5 groups according to the stages of CKD and analyzed the effect of albuminuria. CFVR gradually decreased with an increase in CKD stages. CFVR in patients with albuminuria was lower than those without albuminuria. In groups with CKD stages 2 and 3, the patients with albuminuria showed lower CFVR than those without albuminuria. Multiple logistic regression analysis revealed that albuminuria, age, and gender were independently associated with CFVR impairment. Of these factors, albuminuria was the most powerful predictor with the risk ratio of 12.4 for CFVR impairment. In conclusion, the more the CKD stages progressed, the more severe CFVR was impaired. Albuminuria was associated with CFVR impairment in patients with CKD; even in mild-to-moderate CKD, patients with albuminuria showed further reduced coronary vasodilator capacity.

Peripheral cardiac sympathetic hyperactivity in cardiovascular disease: role of neuropeptides.

High levels of sympathetic drive in several cardiovascular diseases including postmyocardial infarction, chronic congestive heart failure and hypertension are reinforced through dysregulation of afferent input and central integration of autonomic balance. However, recent evidence suggests that a significant component of sympathetic hyperactivity may also reside peripherally at the level of the postganglionic neuron. This has been studied in depth using the spontaneously hypertensive rat, an animal model of genetic essential hypertension, where larger neuronal calcium transients, increased release and impaired reuptake of norepinephrine in neurons of the stellate ganglia lead to a significant tachycardia even before hypertension has developed. The release of additional sympathetic cotransmitters during high levels of sympathetic drive can also have deleterious consequences for peripheral cardiac parasympathetic neurotransmission even in the presence of β-adrenergic blockade. Stimulation of the cardiac vagus reduces heart rate, lowers myocardial oxygen demand, improves coronary blood flow, and independently raises ventricular fibrillation threshold. Recent data demonstrates a direct action of the sympathetic cotransmitters neuropeptide Y (NPY) and galanin on the ability of the vagus to release acetylcholine and control heart rate. Moreover, there is as a strong correlation between plasma NPY levels and coronary microvascular function in patients with ST-elevation myocardial infarction being treated with primary percutaneous coronary intervention. Antagonists of the NPY receptors Y1 and Y2 may be therapeutically beneficial both acutely during myocardial infarction and also during chronic heart failure and hypertension. Such medications would be expected to act synergistically with β-blockers and implantable vagus nerve stimulators to improve patient outcome.

Evaluation of coronary microvascular function and nitric oxide synthase intron 4a/b polymorphism in patients with coronary slow flow

Slow coronary flow (SCF) is reported to be associated with increased risk of cardiovascular disease. We have used coronary flow reserve measurement by transthoracic Doppler echocardiography to determine coronary microvascular function in patients with SCF and to determine whether the intron 4a/b polymorphism of the eNOS gene influences coronary endothelial function. Overall, 96 patients with SCF and 79 controls were enrolled in the study. Coronary flow was quantified according to the thrombolysis in myocardial infarction (TIMI) frame count (TFC) on angiogram. Coronary diastolic peak flow velocities (DPFV) were measured with color Doppler flow mapping at baseline and after dipyridamole infusion. Coronary flow reserve was calculated as the ratio of hyperemic to baseline DPFV. The eNOS 4a/b polymorphism was detected by PCR. Patients with diabetes were excluded from the study. The SCF group was comparable to the control group in terms of demographic and clinical characteristics, except for hemoglobin and HDL-cholesterol levels, TFC of the left anterior descending artery, the circumflex artery, and the right coronary artery; the mean TFC was higher in the SCF group. Hyperemic DPFV and the hyperemic/baseline DPFV ratio were significantly lower in the SCF group when compared with the control group. However, baseline DPFV were similar in both groups. The number of patients with eNOS4 a/a and eNOS4 a/b phenotypes was statistically higher in SCF groups. The frequency of allele 'a' of the eNOS4 gene was also statistically higher in the SCF group. When patients were grouped according to the presence or absence of allele 'a' of the eNOS4 gene, statistically significant differences were found in the TFC of the left anterior descending artery, the circumflex artery; mean TFC; baseline DPFV; and hyperemic/baseline DPFV. Univariate analysis in which eNOS4 b/b was used as the referent group showed that the presence of allele 'a' of the eNOS4 gene significantly predicted SCF (odds ratio: 2.79, 95% confidence interval: 1.32-5.89; P=0.007). In multivariate analysis using a model adjusted for variables with a P value lower than 0.10 in univariate analyses, the presence of allele 'a' of the eNOS4 gene was found to be an independent predictor of SCF (odds ratio: 3.22, 95% confidence interval: 1.28-8.82; P=0.013). The presence of allele 'a' may be a risk factor for microvascular endothelial dysfunction and higher TFCs in SCF patients.

Glycosaminoglycan metabolism defects and atherosclerosis: frequent association of endothelial dysfunction in patients with Mucopolysaccharidosis

Cardiovascular lesions, including coronary artery stenosis, are frequently associated and can cause sudden death in patients with genetic defects of glycosaminoglycan (GAG) metabolism. Early diagnosis of coronary artery lesions is difficult, although potentially lifesaving. Histopathological similarities between atherosclerotic changes in adults and in patients with genetic GAG metabolism defects have been known. Atherosclerosis is the result of a complex process involving metabolism of GAGs and proteoglycans preceded by endothelial dysfunction as a key event. Decreased nitric oxide (NO) bioavailability is considered the hallmark of endothelial dysfunction. Reduced NO synthase (NOS) has been reported in atherosclerotic arteries. Impairment in reactive hyperemia-digital peripheral arterial tonometry (RH-PAT) with EndoPAT has been validated to correlate coronary microvascular function in patients with atherosclerosis. RH-PAT is thought to reflect endothelial NO production. Immunohistological staining of endothelial NOS was performed in the stenotic lesions in the coronary artery of a 3-year-old patient with Mucopolysaccharidosis-I, showing decreased activities. This prompted a study to measure endothelial function in patients with GAG metabolism defects for early diagnosis of endothelial dysfunction in the coronary arteries as an early sign of coronary artery changes. Evaluation by RH-PAT in 30 patients with variable genetic defects in GAG metabolism revealed significantly decreased Reactive Hyperemia Indexes compared with 12 controls. Evaluation of endothelial function with RH-PAT in patients with GAG metabolism defects may detect coronary artery lesions that can be underdiagnosed by the other measures such as coronary angiography. Use of this method may prove vital in the management of patients with GAG metabolism defects.

Correction

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 6, No. 3Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published1 Jun 2013https://doi.org/10.1161/HAE.0b013e318297c2b0Circulation: Arrhythmia and Electrophysiology. 2013;6:e41This article corrects the followingEffects of Iatrogenic Myocardial Injury on Coronary Microvascular Function in Patients Undergoing Radiofrequency Catheter Ablation of Atrial FibrillationIn the article “Effects of Iatrogenic Myocardial Injury on Coronary Microvascular Function in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation” by Lim et al, which was published in the April 2013 issue (Circ Arrhythm Electrophysiol. 2013;6:318-326), a correction was needed.The URL for the Clinical Trial Registration has been updated: http://cris.nih.go.kr.The online version of the article has been corrected. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesEffects of Iatrogenic Myocardial Injury on Coronary Microvascular Function in Patients Undergoing Radiofrequency Catheter Ablation of Atrial FibrillationHong Euy Lim, et al. Circulation: Arrhythmia and Electrophysiology. 2013;6:318-326 June 2013Vol 6, Issue 3 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/HAE.0b013e318297c2b0 Originally publishedJune 1, 2013 PDF download Advertisement

Effects of Iatrogenic Myocardial Injury on Coronary Microvascular Function in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation

Iatrogenic myocardial injury by radiofrequency catheter ablation (RFCA) releases proinflammatory substances from damaged myocardium, and these may contribute to endothelial dysfunction in systemic vascular structure. The aim of this study is to evaluate the effect of nonischemic myocardial damage on coronary microvascular function in patients undergoing atrial fibrillation (AF) ablation. We included 49 patients who underwent AF ablation (paroxysmal AF=25, persistent AF=24) and 34 controls. Immediately before and after RFCA, index of microvascular resistance (IMR) was assessed at left anterior descending coronary artery, and blood samples were obtained for analyses of nitric oxide (NO), activated leukocyte cell adhesion molecule, and lipoprotein-associated phospholipase. Transthoracic echocardiography was performed at baseline, 1 day, 1 month, and 3 months after RFCA. Compared with baseline, IMR, activated leukocyte cell adhesion molecule, and lipoprotein-associated phospholipase increased and NO decreased after RFCA. In 36 subjects with increasing IMR, E/E' ratio increased at 1 day and returned to baseline level at 3 months after RFCA. Changes in activated leukocyte cell adhesion molecule and lipoprotein-associated phospholipase between baseline and after RFCA were independently related to the increase in IMR. In 14 subjects (28.6%), arrhythmia recurred. Using a cutoff value of 9.3 mm Hg/s, sensitivity was 56.7% and specificity was 91.2% for IMR change in predicting AF recurrence (P=0.028). Myocardial damage by RFCA provoked coronary microvascular dysfunction through systemic proinflammatory reaction that may contribute to transient diastolic dysfunction. This phenomenon may represent a mechanism for early recurrence of arrhythmia after RFCA. URL: http://cris.cdc.go.kr. Unique identifier: KCT0000030.

Evaluation of coronary microvascular function in patients with vasospastic angina

To investigate endothelium-dependent and -independent coronary microvascular functions in patients with vasospastic angina (VSA). Thirty-six patients with VSA (30 men and 6 women; mean age, 58 years) were enrolled in this study. VSA was defined as ≥ 90% narrowing of the epicardial coronary arteries on angiography performed during a spasm provocation test, presence of chest pain, and/or ST-segment deviation on an electrocardiogram (ECG). Patients (n = 36) with negative spasm provocation test results and those matched for age and sex were enrolled as a control group (nonVSA group). Low-dose acetylcholine (ACh; 3 μg/min) was infused into the left coronary ostium for 2 min during the spasm provocation test. Following the spasm provocation test, nitroglycerin (0.2 mg) was administered intracoronally. Coronary blood flow (was calculated from quantitative angiography and Doppler flow velocity measurements, and the coronary flow reserve was calculated as the ratio of coronary flow velocity after injection of adenosine triphosphate (20 μg) to the baseline value. Changes in the coronary artery diameter in response to ACh and nitroglycerin infusion were expressed as percentage changes from baseline measurements. Body mass index was significantly lower in the VSA group than in the nonVSA group. The frequency of conventional coronary risk factors and the rate of statin use were similar between the 2 groups. The left ventricular ejection fraction as evaluated by echocardiography was similar between the 2 groups. The duration of angina was 9 ± 2 mo. The results of blood chemistry analysis were similar between the 2 groups. Low-dose ACh did not cause coronary spasms. The change in coronary artery diameter in response to ACh was lower in the VSA group (-1.4% ± 9.3%) than in the nonVSA group (3.1% ± 6.5%, P < 0.05), whereas nitroglycerin-induced coronary artery dilatation and coronary blood flow increase in response to ACh or coronary flow reserve did not differ significantly between the 2 groups. These findings suggest that microvascular coronary function may be preserved despite endothelial dysfunction of the epicardial coronary arteries in patients with VSA.

Coronary Microvascular Function in Patients With Isolated Systolic and Combined Systolic/Diastolic Hypertension

Isolated systolic hypertension (ISH) is a common condition in the elderly that is associated with endothelial dysfunction. Concerning the effect of type of hypertension on coronary microvascular function, coronary flow reserve (CFR) in patients with ISH was evaluated and the results were compared with patients with combined systolic/diastolic hypertension (SDH). Seventy-six elderly patients (older than 60 years) who were free of coronary artery disease and diabetes mellitus were enrolled in the study (38 with ISH and 38 with combined SDH). Using transthoracic Doppler echocardiography, CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities. A CFR value of >2 was accepted as normal. The mean age was 68.6±6.3 years and the groups had similar features with regard to demographic and clinical characteristics. Patients with ISH had significantly lower CFR values compared with those with combined SDH (2.22±0.51 vs 2.49±0.56, respectively; P=.03). On multivariate regression analysis, ISH (β=-0.40, P=.004) and dyslipidemia (β=-0.29, P=.04) were the independent predictors of CFR. These findings indicate that CFR, an indicator of coronary microvascular/endothelial function, is impaired more profoundly in patients with ISH than in patients with combined SDH.

Coronary microvascular function in patients with Cushing’s syndrome

The aim of the study was to evaluate patients with Cushing's syndrome the coronary flow reserve (CFR), an index of coronary microvascular function. Fifteen newly diagnosed patients with Cushing's syndrome (1 male/14 females; mean age 45 ± 11 years), were selected for having no clinical evidence of ischemic heart disease. Twelve patients had pituitary-dependent Cushing's disease and three had an adrenal adenoma. Fifteen subjects matched for age, sex, and major cardiovascular risk factors were used as controls. Coronary flow velocity in the left anterior descending coronary artery was investigated by transthoracic Doppler echocardiography at rest and during adenosine infusion. CFR was obtained as the ratio hyperemic/resting diastolic flow velocity. A reduced coronary reserve (hyperemic/resting ratio ≤ 2.5) was found in 5/15 Cushing patients and 4/15 controls. In all patients with abnormal CFR, epicardial coronary stenosis was excluded by multi-slice computed tomographic coronary angiography. CFR was inversely related to urinary cortisol in patients with endogenous hypercortisolism (Spearman's rho = -0.57, P = 0.03), while no correlation was found in controls. Coronary microvascular function, as assessed by CFR, is pathologically reduced in a considerable number of patients with Cushing's syndrome without clinical symptoms of ischemic heart disease and in the absence of epicardial coronary artery lesions, as well as in controls matched for cardiovascular risk factors. The presence of comorbidities can explain this early coronary abnormality in both patients and controls. Whether urinary cortisol may be a predictor of coronary microvascular function in the setting of patients with Cushing's syndrome, needs further investigation.

Elevated mean platelet volume is associated with impaired coronary microvascular function in patients with idiopathic dilated cardiomyopathy

Attenuated coronary flow reserve (CFR) has been reported in patients with idiopathic dilated cardiomyopathy (IDC). On the other hand increased platelet activity has been demonstrated in patients with congestive heart failure and left ventricular dysfunction. Accordingly, we aimed to investigate whether mean platelet volume (MPV) is increased in patients with IDC and increased MPV correlates with the degree of coronary microvascular dysfunction.MPV was measured in 37 patients with IDC. Each patient with IDC also underwent echocardiographic examination including CFR measurement. Patients with IDC were divided into two groups based on median CFR value (lower CFR group and normal CFR group).MPV was significantly higher in the lower CFR group than in the normal CFR group (9.00 ± 0.56 vs. 8.25 ± 0.76 fl; respectively, p = 0.001). CFR correlated significantly and inversely to MPV (r = −0.475, p = 0.003). Logistic regression analysis revealed that MPV level was the independent predictor of lower CFR (β = −0.750, p = 0.002). Furthermore, MPV was an accurate predictor of low CFR (p = 0.001); Area under the curve was 82% (95% CI 0.67–0.96). The best cut-off value of MPV to predict low CFR was 8.3 fl with 95% sensitivity and 69% specificity.In conclusion, the present study showed a negative correlation between MPV and CFR in patients with IDC.

Quantitative assessment of coronary microvascular function in patients with and without epicardial atherosclerosis

The influence of atherosclerosis and its risk factors on coronary microvascular function remain unclear as current methods of assessing microvascular function do not specifically test the microcirculation in isolation. We examined the influence of epicardial vessel atherosclerosis on coronary microvascular function using the index of myocardial resistance (IMR).IMR (a measure of microvascular function) and fractional flow reserve (FFR, a measure of the epicardial compartment) were measured in 143 coronary arteries (116 patients). Fifteen patients (22 arteries, mean age 48+/-16 years) had no clinical evidence of atherosclerosis (control group). One hundred and one patients (121 arteries, mean age 63+/-11 years) had established atherosclerosis and multiple cardiovascular risk factors (atheroma group). Mean IMR in the control group (19+/-5, range 8-28) was significantly lower than in the atheroma group (25+/-13, range 6-75) (P<0.01). However, there was large overlap between IMR in both groups, with 69% of IMR values in patients with atheroma being within the control range. Mean FFR was also higher in the control group (0.96+/-0.02, range 0.93-1.00) than in the atheroma group (0.85+/-0.14, range 0.19-1.00) (P<0.01). There was no correlation between IMR and FFR (r=0.09; P=0.24), even when results in the control (r=0.02; P=0.92) and atheroma (r=0.15; P=0.10) groups were analysed in isolation. Using stepwise multiple regression analysis presence/absence of atheroma (ss=0.42; P=0.02) was the only independent determinant of IMR.Mean IMR is higher in patients with epicardial atherosclerosis. However, there is a large overlap between IMR in patients with and without epicardial atherosclerosis.