Usefulness of coronary flow reserve measured by transthoracic coronary Doppler ultrasound in the elderly

The left anterior descending （LAD） coronary artery is the main vessel of human coronary circulation, and life-threa- tening consequences are seen when flow in this area is im- paired, Noninvasive measurement of coronary flow re- serve （CFR）, defined as the ratio of maximal to baseline coronary blood flow, has been repeatedly shown to be a feasible technique by ultrasound transthoracic Doppler （TTD） both in the LAD and, with some limitations, in the posterior descending （PD） coronary artery.

IN PATIENTS WITH HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY AND CORONARY HEART DISEASE,CORONARY FLOW RESERVE IS SIMILARLY IMPAIRED

Coronary blood flow reserve (CFR) was assessed by transesophageal Doppler echocardiography in normal subjects (group A. n=20),hypertensive non-left ventricular hypertrophy (non-LVH)Patients (group B,n=22). hypertensive patients with LVH(group C.n=32)and coronary heart disease patients (group D. n=33) with the volume sample placed at the bifurcation of the left main and left main and left descending coronary artery. Coronary blood flow velocity (CBFV)was evaluated at rest.2 minutes after dipyridamole (0. 56mg/kg. i. v.) . and 2 minutes after aminophylline i.v. The ratio of dipyridamole to rest maximal diastolic velocity (D/R PDV) was considered the index of coronary blood flow reserve.It was found that D/R PDV was significantly less in groups C and D compared with that in groups A and B (D PDC,1.84±0. 57. 1. 57±0. 41 versus 2.59±0.70 and 2.22+0.58,respectively),with no difference in D/R PDV between groups C and D.Twenty-four out of 32 patients in group C with D/R PDV were less than 2.0 compared to 29 out of 33 patients in group D (P>0.05).Significant negative correlation was found between D/R PDV. D/R PSV and interseptal thickness. left ventricular mass index in hypertensive patients.These data show that impaired CFR in hypertensive patients with LVH is comparable to that in patients with coronary heart disease.

Impact of uncontrolled blood pressure on diagnostic accuracy of coronary flow reserve for detecting significant coronary stenosis in hypertensive patients

Background Impaired coronary flow reserve （CFR） in patients with hypertension may be caused by epicardial coronary stenosis or microvascular dysfunction. Antihypertensive treatment has been shown to improve coronary microvascular dysfunction. The aim of this study was to evaluate the impact of uncontrolled blood pressure （BP） on diagnostic accuracy of CFR for detecting significant coronary stenosis. Methods A total of 98 hypertensive patients scheduled for coronary angiography （CAG） due to chest pain were studied. Of them, 45 patients had uncontrolled BP （defined as the office BP 〉140/90 mmHg （1 mmHg=0.133 kPa） in general hypertensive patients, or ≥130/80 mmHg in hypertensive individuals with diabetes mellitus）, and the remaining 53 patients had well-controlled BP. CFR was measured in the left anterior descending coronary artery （LAD） during adenosine triphosphate-induced hyperemia by non-invasive transthoracic Doppler echocardiography （TTDE） within 48 hours prior to CAG. Significant LAD stenosis was defined as 〉70% luminal narrowing. Diagnostic accuracy of CFR for detecting significant coronary stenosis was analyzed with a receiver operating characteristic analysis. Results CFR was significantly lower in patients with uncontrolled BP than in those with well-controlled BP （2.1±0.6 vs. 2.6±0.9, P〈0.01）. Multivariate linear regression analysis of the study showed that the value of CFR was independently associated with the angiographically determined degree of LAD stenosis （β= -0.445, P 〈0.0001） and the presence of uncontrolled BP （β= -0.272, P=0.014）. With a receiver operating characteristic analysis, CFR 〈2.2 was the optimal cut-off value for detecting LAD stenosis in all hypertensive patients （AUC 0.83, 95% CI 0.75-0.91） with a sensitivity of 75%, a specificity of 78%, and an accuracy of 77%. A significant reduction of diagnostic specificity was observed in patients with uncontrolled BP compared with those with well-controlled BP （67% vs. 93%, P=0.031）. Conclusions CFR measurement by TTDE is valuable in the diagnosis of significant coronary stenosis in hypertensive patients. However, the diagnostic specificity is reduced in patients with uncontrolled BP.

Effects of hypoxia on coronary flow reserve as determined by myocardial contrast echocardiography in swine

Background Time-intensity curves derived from microbubble destruction/refilling sequences and recorded using myocardial contrast echocardiography (MCE) can provide parameters that correlate with coronary blood flow. The response of these parameters to adenosine vasodilatation correlates with coronary flow reserve (CFR) measured by fluorescent microsphere techniques (FMT). Currently, no data exist regarding the effect of physiological variables, such as hypoxia, on the determination of CFR by MCE. The purpose of this study was to define the effects of decreases in blood partial pressure of oxygen (PO_2) on CFR as measured by MCE. Methods Studies were performed in 9 closed chest swine. Low-energy, real-time MCE was performed with commercial instruments in short axis view at papillary muscle level while infusing BR_1 at 30 ml/h. High-energy ultrasound bursts (referred to as FLASH frames) destroyed the bubbles every 15 cardiac cycles, and resultant time-intensity curves derived from these sequences were fitted to the exponential function y = A (1-e -bt) +c, from which the rate of signal rise (b) was obtained. CFR was calculated as the ratio of b values after adenosine infusion to baseline and was obtained during the control period and after decreasing blood PO_2 by giving nitrogen via a respirator to create artificial hypoxic conditions. CFR was independently determined by FMT. Results Nitrogen led to significant decreases in mean PO_2, from (120.6±18.9) mmHg to (51.8±15.9) mmHg (P<0.01). Adenosine produced a similar increase in CFR (2.5 fold vs 3.1 fold) as assessed by MCE and FMT during the control period. The decrease in PO_2 post nitrogen resulted in a slight increase in values at rest: 0.46±0.15 to 0.53±0.18 for b and (1.39±0.66) ml·min -1·g -1 to (1.72±0.30) ml·min -1·g -1 for myocardial blood flow (MBF) (both P<0.05). In addition, values decreased in response to adenosine using both techniques: 1.05±0.35 to 0.82±0.27 for b and (4.30±3.16) ml·min -1·g -1 to (3.93±1.27) ml·min -1·g -1 for MBF (both P<0.05). Thus, CFR was markedly reduced under hypoxic conditions, to 1.4 by MCE (P<0.05 compared with the baseline), and to 2.5 by FMT (P>05 compared with the baseline). Conclusions CFR values diminish under hypoxic conditions according to both MCE and FMT. The reductions in CFR involve both an increase in resting values and a decrease in post adenosine measurements, as determined by both techniques. The reduction in CFR under hypoxia is slightly greater using MCE than using FMT. Physiological variables, such as hypoxia, must be taken into consideration when assessing CFR by MCE.

Impact of blood pressure control on coronary flow reserve in hypertensive patients

Objective To investigate the impacts of blood pressure control on coronary flow reserve(CFR)in hypertensive patients.Methods A total of 236 patients without significant coronary stenosis(defined as<50%luminal narrowing confirmed by coronary angiography or coronary artery CT scan)between January 2011 and July 2015were retrospectively enrolled in this study.CFR

Assessment of Coronary Flow Velocity Reserve by Noninvasive Transthoracic Doppler Echocardiography in Patients with Angiographically Normal Coronary Arteries

Summary： The measurement of coronary flow velocity reserve （CFVR） by transthoracic Doppler echocardiography （TTDE） with invasive intracoronary Doppler flow wire technique （ICD） was validated and the pathological factors which influence CFVR in patients with angiographically normal coronary arteries were analyzed. CFVR was determined successfully in left anterior descending artery （LAD） in 37 of 40 patients with angiographically normal coronary arteries （men 22, women 15, age 20-75 years, mean age 54±12 years）. Coronary flow velocity was measured in the distal LAD by TTDE with contrast enhancement at baseline and during intravenous adenosine infusion of 110 μg/ kg per min within 48 h after ICD technique. Average peak velocity at baseline （APVb）, average peak velocity during hyperemia （APVh） and CFVR determined from TTDE were correlated closely with those from ICD measurements （APVb： y= 0. 64x＋ 5. 04, r=0. 86, P〈0. 001; APVh： y=0. 63x＋14. 36, r=0.82, P〈0.001; CFVR： y=0.65xq-0.92, r=0.88, P〈0.001）. For CFVR measurements, the mean differences between TTDE and ICD methods were 0. 12±0.39. CFVR in patients with history of hypertension was significantly lower than that in patients without history of hypertension （P〈0.05）. Intravascular ultrasound （IVUS） was performed in 34 patients. Plaque formation was found in LAD by IVUS in 17 （50%） patients. No significant difference in CFVR was found between the patients without plaque formation （3. 11±0. 49） and those with plaque formation （2. 76±0.53, P=0. 056）. It is suggested that TTDE with contrast enhancement provides reliable measurement of APV and CFVR in the distal I.AD. The early stage of atherosclerosis could be detected by IVUS, which may be normal in angiography. CFVR is impaired in patients with history of hypertension compared with that in patients without history of hypertension.

Non-invasive Assessment of Coronary Flow Velocity Reserve: A New Method Using Transthoracic Doppler Echocardiography

Summary: Transthoracic Doppler echocardiography (TTDE) allows noninvasive flow measurement in the distal left anterior descending artery (LAD). The feasibility of detecting coronary flow by contrast-enhanced TTDE with second harmonic technique was assessed, the coronary flow velocity reserve (CFVR) was evaluated in comparison to intracoronary Doppler flow (ICD) analysis and the CFVR after PTCA in LAD was investigated. In 77 (96 %) of 80 patients, CFVR was successfully determined with intravenous adenosine infusion. Doppler signal quality was evaluated in the first 46 patients by use of intravenous Levovist infusion and second harmonic technique. The Doppler flow was not visible in 1 patient only. CFVR determined from TTDE (2.77±0.65) was correlated closely with those from ICD (2.88±0.78) measurements (y=0.73x+0.67, r=0.87, P<0.001). In conclusion, TTDE is a feasible method and provides reliable data on CFVR which can be used for follow-up after PTCA.

RELATIONS OF ENDOTHELIAL FUNCTION AND BLOOD FLOW IN BRACHIAL ARTERY AND CORONARY ARTERY

Objective:To determine the relations between endothelium-dependent vasodilator function and blood flow in the brachial and coronary arteries in patients with suspected coronary artery disease.Methods:Twenty-eight patients with suspected coronary artery disease underwent brachial artery endothelial function test by using high-resolution B-mode ultrasound before coronary angiography(CAG)and coronary flow reserve(CFR)test by using intracoronary Doppler technique.The correlation of coronary artery dilatation induced by an increase in blood flow after intracoronary adenosine infusion and brachial artery flow-mediated dilatation(FMD) following reactive hyperemia was evaluated.The relation between the change of brachial artery blood flow and CFR was also studied.Results:There was a positive correlation between brachial FMD and percent change of coronary diameter after adenosine infusion(12.50%±9.35% vs 11.38%±7.55%,r=0.425,P=0.02).There was also a weak negative relation between brachial flow change following reactive hy-peremia and CFR(r=-0.397,P=0.04).Conclusion:There is a correlation between the coronary endo-thelial function and the CFR by ultrasonic determination of brachial flow changes following reactive hyperemia.

Deferred revascularization in diabetic patient according to combined invasive functional and intravascular imaging data:A case report

BACKGROUND Invasive functional evaluation by fractional flow reserve(FFR)is considered as a gold standard for the evaluation of intermediate coronary stenosis.However,in patients with diabetes due to accelerated progression of atherosclerosis the outcome may be worse even in the presence of negative functional testing.CASE SUMMARY We present a case of 55-year-old male diabetic patient who was admitted for chest pain.Diagnostic coronary angiography disclosed 2 intermediate stenoses of the obtuse marginal branch with no evidence of restenosis on previously implanted stent.Patient undergone invasive functional testing of intermediate lesion with preserved FFR(0.88),low coronary flow reserve(1.2)and very high index of microvascular resistance(84).Due to discrepancy in invasive functional parameters,intravascular imaging with optical coherence tomography showed fibrotic stenoses without signs of thin-sup fibroatheroma.Because of the preserved FFR and no signs of vulnerable plaque,the interventional procedure was deferred and the patient continued with optimal medications.CONCLUSION Combined functional and anatomic imaging of intermediate coronary stenosis in diabetic patients represent comprehensive contemporary decision pathway in the management of the patients.

Coronary physiology assessment in the catheterization laboratory

Physicians cannot rely solely on the angiographic appearance of epicardial coronary artery stenosis when evaluating patients with myocardial ischemia. Instead, sound knowledge of coronary vascular physiology and of the methods currently available for its characterization can improve the diagnostic and prognostic accuracy of invasive assessment of the coronary circulation, and help improve clinical decision-making. In this article we summarize the current methods available for a thorough assessment of coronary physiology.

Relationship between fibrinogen and fractional flow reserve in coronary intermediate lesions

Objective To study the relationgship and the clinical significance between plasma fibrinogen and fractional flow reserve(FFR)in coronary intermediate lesions.Methods The patients were from The Department of Cardiovascular of Affiliated Hospital of Xuzhou Medical College.Their coronary artery lesions were assessed by

ATP Stress Myocardial Contrast Echocardiography Assessment of Coronary Microvascular Disease with Spasmodic Characteristics: A Case Report

Here, a patient with chest pain and <50% stenosis on coronary angiography, where ATP stress myocardial contrast echocardiography (MCE) revealed that coronary flow reserve was reduced to 1.71 was presented. Perfusion delay occurred in the left ventricular wall of the apex of the heart before ATP stress, and the perfusion delay area was significantly reduced at peak stress. Similar to the characteristics of "reverse redistribution" of radionuclide myocardium perfusion in coronary vasospasm, the delayed perfusion area in the recovery period was larger than that detected before stress. Together with increased spectral resistance of the distal segment of left anterior descending coronary artery and chest pain, these findings indicated coronary microvascular disease with spasmodic characteristics in this patient. The perfusion characteristics on ATP stress determined by MCE and changes in coronary spectrum have value for the diagnosis and treatment of coronary microvascular disease with spasmodic characteristics.

Higher serum angiopoietin 2 levels are independently associated with coronary microvascular dysfunction in patients with angina in the absence of obstructive coronary artery disease

Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study.Coronary flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography.The patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values<2.5 and the preserved CFR group with CFR values≥2.5.Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay.Independent predictors for impaired CFR were identified by binary logistic regression analysis.The receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P<0.001),and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR.Serum Ang-2 levels were negatively correlated with CFR(r=0.386,P<0.001).Binary logistic regression analysis showed that Ang-2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired CFR.Furthermore,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P<0.001).The area under the curve was 0.712(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.

Prognostic Value of Gai＇s Plaque Score and Agatston Coronary Artery Calcium Score for Functionally Significant Coronary Artery Stenosis

Background： The prognostic valtles of the coronary computed tornography angiography （CCTA） score for predicting future cardiovascular events have been previously demonstrated in numerous studies. However, few studies have used the rich information available from CCTA to detect functionally significant coronary lesions. We sought to compare the prognostic values of Gai＇s plaque score and the coronary artery calcium score tCACS） of CCTA for predicting functionally significant coronary lesions, using fractional flow reserve （FFR） as the gold standard. Methods： We retrospectively analyzed 107 visually assessed significant coronary lesions in 88 patients （mean age, 59.6 ± 10.2 years： 76.14% of males） wino underwent CCTA, invasive coronary angiography, and invasive FFR nneasurement. An FFR 〈0.80 indicated hemodynamically significant coronary stenosis. Lesions were divided into two groups using an FFR cutoffvalue of 0.80. We compared Gai＇s plaque scores and CACS between the two groups and evaluated the correlations of these scores with FFR. The statistical methods included unpaired t-test, Mann-Whitney U-test, and Spearman＇s correlation coefficients. Results： Coronary lesions with FFR 〈0.80 lind Inigtner Gai＇s scores than those with FFR 〉0.80. Gai＇s score had the strongest correlation with FFR （r= 0.48, P 〈 0.01 ） and lind a greater area under tlne curve 0.72 （95% confidence interval： 0.61 0.82： P 〈 0.01 ） than the CACS of whole arteries and a single artery. Conelusions： Botin CACS in a single artery and Gai＇s plaque score demonstrated a good capacity to assess functionally significant coronary artery stenosis when compared to the gold standard FFR. However, Gai＇s plaque score was more predictive of FFR 〈0.80. Gai＇s score cain be easily calculated in daily clinical practice and could be used when considering revascularization.