Coronary Flow Reserve In LAD Research Articles

Speckle tracking echocardiography allows for the detection of subclinical myocardial dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement

Abstract Background Speckle tracking echocardiography (STE) is helpful for the detection of subclinical systolic function abnormalities. Coronary flow reserve (CFR) measured by dynamic 99mTc-MIBI SPECT-CZT gamma camera allows the diagnosis of myocardial perfusion defects in patients with suspected coronary artery disease (CAD). Purpose The aim of our study is to assess the diagnostic value of STE and SPECT-based CFR in patients with suspected coronary artery disease (CAD). Methods 85 patients (pts) (37.6% females, mean age 65.4 ± 8.5 years) with suspected CAD underwent 2D and 3D STE, as well as myocardial perfusion study with novel solid-state CZT nuclear camera (dipyridamole stress protocol). We calculated global longitudinal left ventricular strain (GLS), as well as LS of individual coronary artery territories (LAD LS, Cx LS and RCA LS). Total CFR and CFR in three coronary territories were also measured. The presence of CAD (coronary artery stenosis > 70%) was assessed by coronary angiography. Results Significant CAD was confirmed in 50 patients. Mean total CFR (1.71 ± 0.61 vs 2.1 ± 0.52, p = 0.002), as well as CFR in LAD territories (1.54 ± 0.68 vs 1.91 ± 0.56, p = 0.02), RCA territories (1.58 ± 0.82 vs 1.95 ± 0.68, p = 0.048) and Cx territories (1.58 ± 0.78 vs 2.08 ±0.76, p = 0.01) were lower in pts with CAD. In the ROC curve analysis of total CFR for the diagnosis of CAD the AUC was found to be 0.7 (p = 0.001). Mean absolute 2D GLS in pts with total CFR < 2.0 was significantly lower than in pts with CFR >= 2.0 (-14.5 ± 4.3 vs -16.9 ± 3.4, p = 0.005). Similar differences were observed in all three coronary territories (p ≤ 0.05). The same results were not observed in case of 3D GLS . Modest but significant correlations were detected between total CFR and 2D GLS values (r = -0.38; p < 0.001), LAD CFR and 2D LAD LS (r = -0.33; p = 0.002), LCx CFR and 2 D LCx LS (r = -0.39; p < 0.001), total CFR and EF (r = 0.36; p < 0.001). GLS at rest had good diagnostic value for detecting total CFR < 2 (AUC= 0.7; p = 0.004). The criterion with the highest diagnostic accuracy was GLS > (- 18.5) – its sensitivity was 84%, specificity 42%, positive predictive value 0.7, negative predictive value 0.7 and overall accuracy 66%. Conclusions CFR assessed by SPECT provides acceptable diagnostic accuracy for the detection of significant CAD. STE allows for identification of patients with subclinical dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement.

Abstract 17001: Enhancing Coronary Functional Angiography: Integrating Doppler-Based Left Circumflex Coronary Flow Reserve in Assessment

Background: Coronary microvascular dysfunction (CMD), predominantly affecting women is associated with poor outcomes and has limited diagnostic options. Coronary functional angiography (CFA) is used for diagnosing CMD in patients with refractory angina and no obstructive coronary artery disease (ANOCA). The assumption is that endothelial-independent CMD is a homogenous disease process, therefore current gold-standard for diagnosis is measure of coronary flow reserve (CFR) in the proximal left anterior descending artery (LAD). However, there is limited data on CFR in the left circumflex (LCx). Objective: Examine the benefits of measuring CFR using Doppler-tipped guide wire in LCx in addition to proximal LAD. Methods: Examined 191 ANOCA patients with Canadian Cardiovascular Society (CCS) class 3 or 4 angina despite optimal medical treatment who underwent CFA for assessment of CMD. CFR measurements were obtained using Doppler-tipped guidewire during the administration of 72 mcg of adenosine in both the proximal LAD and LCx and CFR of <2.5 was used to define CMD. Results: 191 patients underwent CFA including 91% female with a median age of 59 years (IQR: 50, 67). The correlation in CFR measurements between the proximal LAD and LCx was 0.610 (p<0.001). 149 (78%) patients had concordant results including 113 (59%) with abnormal CFRs and 36 (19%) with normal CFRs in both vessels. 12 (6%) had abnormal proximal LAD CFR and normal LCx CFR; and 30 (16%) had an abnormal LCx CFR and normal proximal LAD CFR and would have gone undiagnosed without measuring LCx CFR. Conclusion: The addition of LCx CFR measurement to the current standard CFA protocol using the Doppler guidewire improves diagnosis of CMD in patients. Further studies are needed to evaluate a comprehensive assessment of CMD including measurement of LCx CFR.

Lp(a) and evolution of left anterior descending velocity reserve in stable coronary artery disease: Is there anything beyond dobutamine stress echo outcome?

Abstract Funding Acknowledgements Type of funding sources: None. Background Elevated Lp(a) is related with premature and accelerated atherosclerosis, thus confering increased risk for incident chronic coronary disease (CAD) and adverse outcome. Dobutamine stress echo (DSE) and coronary flow reserve (CFR) are both related with incident CAD and outcome as well. Purpose Aim of the study was to evaluate the potential relationship between Lp(a) and DSE outcome/left anterior descending (LAD) based CFR in chronic CAD. Methods 132 consecutive pts (age 59±11years, 18 females, 33 diabetics) with stable CAD were studied by DSE with a concomitant evaluation of LAD CFR. Lp(a) distribution was positive skewed (median 18.6 mg/dL) and it was then normalized by log transformation (logLpa: 2.9±1.1). High and low Lpa groups (LpaH/LpaL: 30/92) were defined using the conventional cut off 50 mg/dL. Sixty-eight/132 pts had a follow up DSE with concomitant revaluation of CFR at 98±74 months. Absolute and % changes (%d) of LAD CFR were estimated. Results LpaH and LpaL groups had similar baseline: CFR (2.4±0.5 vs 2.4±0.6), %dCFR (0.33±0.7 vs 0.35±0.8), creatinine (0.98±0.18 vs 1.0±0.26), HbA1c (5.3±0.9 vs 5.3±1.0) and high sensitivity C reactive protein (2.8±2.7 vs 2.6±2.8mg/L). LpaH had lower baseline LDL (93±31 vs 111±50 p = 0.04). LpaH and LpaL groups had also similar hemodynamic burden at DSE and incidence of positive DSE. LpaH nondiabetics had a trend for more nonLAD distribution of ischemia (odds ratio=1.8, p = 0.07) with a greater incidence of previous revascularization (odds ratio=2.3, p = 0.03). Further clustering based on optimal CAD treatment achieved at baseline (guidelines achieved optimal resting heart rate and LDL) did not change the findings. However, improvement in %d LAD CFR during follow up was inversely related with logLpa (figure: R2=0.09 p = 0.05). A similar trend for %d LAD CFR and logLpa was evident for a follow up period shorter than 100 months. Conclusion In chronic CAD, high Lpa levels in the absence of diabetes are related with greater incidence of DSE ischemia. Despite similar CFR baseline values between conventionally defined high and low Lpa groups, the evolution of LADCFR during long term follow up is affected consistently on time by the baseline logLpa. These findings support a potential role of Lpa on ischemic burden and microvascular function in the time domain of CAD.

Inflammation and coronary flow reserve in chronic stable coronary artery disease: Evidence for a long standing interplay

Abstract Funding Acknowledgements Type of funding sources: None. Background Low grade inflammation is involved in pathogenesis of ischemia and outcome in coronary artery disease (CAD). Dobutamine stress echo (DSE) and coronary flow reserve (CFR) are both related with incident CAD and respective outcome as well. Purpose To evaluate the potential relationship between inflammation, evaluated by high-sensitivity C-reactive protein as surrogate, and DSE outcome/left anterior descending artery (LAD) CFR in stable chronic CAD. Methods We studied 132 consecutive pts (age 58±12years, 18 females, 33 diabetics) with stable CAD, by DSE with concomitant evaluation of LAD CFR. A cut off 3 mg/dL was used to define high and low CRP groups (CRPH/30pts, CRPL/92pts). CRP distribution was positive skewed (median 1.7mg/l) and CRP was then normalized by log transformation (CRP 0.72±0.9, logCRP 3.2±3.3). Sixty-three out of 132 pts had a follow up DSE with a concomitant reevaluation of CFR at 98±74 months. Absolute and % changes of CFR were estimated. Results CRPH and CRPL groups had similar baseline: CFR (CRPH: 2.3±0.6, CRPL: 2.4±0.6mg/dl), creatinine (1.0±0.2 vs 1.1±0.4mg/dl), HbA1c (5.4±1.0 vs 5.6±1.3%) and LDL (109±46 vs 102±35mg/dl). CRPH and CRPL groups had also similar hemodynamic burden at DSE and incidence of positive DSE. dCFR and %dCFR were lower in CRPL (0.20±0.70 vs 0.69±0.92, p = 0.02 and 0.13±0.33 vs 0.46±0.67 p = 0.01). Further clustering based on optimal CAD treatment achieved at baseline (guidelines defined optimal resting heart rate and LDL) did not change the findings. CFR was inversely related with logCRP (figure 1: r=-0.21, p = 0.04) and creatinine (r=-0.18 p = 0.05). Moreover, during follow up the improvement in CFR (%dCFR) was related with baseline logCRP (figure 2: r=0.30 p = 0.03). In stepwise logistic regression analysis for prediction of a CFR>2, including categorical classification of CRP (>3), diabetes, LDL (>80), Lpa(>50) and resting heart rate, then only CRP>3 classification was finally selected (exp(B)=0.38, p = 0.01). Conclusion Inflammation activity evaluated by CRP in stable CAD is related with the estimated LAD CFR irrespectively from the DSE outcome, both at baseline evaluation as well as dynamically during a long term follow up. The relationship is independent from LDL, Lpa levels and diabetic substrate, thus implying a strong pathophysiological interplay.

Dobutamine 3D strain in the left anterior descending subtended ventricular territory: evidence for relationship with the respective velocity flow reserve

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Three dimensional speckle tracking imaging (3DST), provides an evolving means to interrogate left ventricular (LV) function. However, its clinical application still remains limited. Purpose Purpose of the study was to interrogate the relationship between regional deformation by 3DST in left anterior descending artery (LAD) subtended territory and the respective coronary flow reserve (CFR). Methods Fifty patients aged 63 ± 6 years with chronic coronary syndromes were studied. Patients had no evidence of dobutamine (DOB) induced ischemia in LAD territory. Distal LAD CFR was estimated by adenosine Doppler echo (140mg/kg/min). 3DST derived integral strain (IS) and respective components (longitudinal -LS, circumferential –CS, radial -RS) were estimated by a full volume sweep (3.5 MHz sector probe) at >20 volumes/sec. A 16 LV sectors (sc) polar map was provided (Artida,Toshiba) with 10/16 sectors (sc) analysed, 6 sc being the conventional LAD territory (sc: 3,4,5,6,7,8) and another 4 sc being adjacent ones (sc: 1, 2, 9, 10). 3D datasets acquired at rest (R) and low dose DOB (20mg/kg/min). LV mass was automatically measured from volumetric data sets and its variability during cardiac cycle was considered as an index of coherence for true LV borders recognition. Results CFR was >2 in all pts (range 2.0-4.2, 2.74 + 0.46). Mean variability of LV mass between R and DOB was 0.044 (range: -0.090-0.008, p = ns). 3DST strain was related with LAD CFR as follows: 1.For IS: at R: sc1: r = 0.38, p = 0.023, sc3: r = 0.44, p = 0.006, sc5: r = 0.35, p = 0.03, sc9: r = 0.50, p = 0.002. At DOB sc7: r = 0.31, p = 0.05. 2.For LS: at R: sc5: r=-0.40, p = 0.01. 3.For CS: at R: sc5: r=-0.33, p = 0.02, sc5: r=-0.46, p = 0.004. 4.For RS: at R: sc9: r=-0.38, p = 0.08. The % changes of regional IS post DOB compared to R were also related with CFR LAD in the sectors sc1 and sc3 (r = 0.34, p = 0.05, and p = 0.40, p = 0.002 respectively). Conclusion 3DST derived LV deformation indices in the LAD territory are related with the respective CFR. LV regional integral strain has a stronger relationship with LAD CFR when compared to the partial vectors. The 3DST derived deformation indices seem sensitive enough to reproduce the flow function relationship in the LAD territory. Thus, potential applicability has to be supported.

Left ventricular longitudinal strain impairment at rest correlates with reduction of SPECT-derived coronary flow reserve in patients with suspected coronary artery disease

Abstract Background Speckle tracking echocardiography (STE) may be useful for the detection of subclinical systolic function abnormalities. Dynamic acquisition of myocardial blood flow using 99mTc-MIBI SPECT-CZT gamma camera allows the calculation of coronary flow reserve (CFR). Purpose The aim of our study is to assess the relationship between left ventricular longitudinal strain (LS) and CFR in patients with suspected coronary artery disease (CAD). Methods 55 patients (pts) (43.6% females, mean age 64.6±8.4 years) with suspected CAD underwent transthoracic echocardiography with assessment global and local LS by STE. We calculated mean global left ventricular LS (GLS), as well as LS of individual coronary artery territories (LAD LS, LCx LS and RCA LS). All pts underwent myocardial perfusion study with novel solid-state CZT nuclear camera (dipyridamole stress protocol). We measured CFR of the left ventricle and individual coronary territories. Results Mean absolute GLS in pts with total CFR <2 was significantly lower than in pts with CFR >2 (median value −13.9 vs −18.3; p<0.001). Similar differences were observed in all three coronary territories (p≤0.01). Modest but significant correlations were detected between total CFR and GLS values (r=−0.56; p<0.001), LAD CFR and LAD LS (r=−0.54; p<0.001), RCA CFR and RCA LS (r=−0.36; p=0.007), LCx CFR and LCx LS (r=−0.53; p<0.001). GLS at rest had good diagnostic value for detecting total CFR <2 (AUC=0.767; p<0.001). The criterion with the highest diagnostic accuracy was GLS > (−15.8) – its sensitivity was 68%, specificity 77.7%, and overall accuracy 73%. Conclusions Indices of left ventricular longitudinal function obtained by speckle tracking echocardiography correlate with SPECT-derived CFR in patients with suspected CAD. Funding Acknowledgement Type of funding sources: None.

Serial Assessment of Transthoracic Coronary Flow Reserve as Method of Assessing Efficacy of Intracoronary Intervention in the Left Anterior and Posterior Descending Arteries

The study group comprised 14 patients with single-vessel coronary disease (stenosis 82+/-14%) of the LAD (9 patients) or right coronary artery (RCA, 5 patients) scheduled for stent implantation. All patients underwent dipyridamole stress echo with CFR evaluation of either distal LAD or PDA 1 day before and 6-9 days after successful stent implantation. CFR was calculated as the ratio of hyperemic to basal peak diastolic velocity. A CFR value of <2.0 was considered abnormal. Adequate Doppler signals to measure CFR were obtained in 13 patients (93%). Abnormal pre-procedure CFR value was revealed in 12 assessed patients (92%). Significant increase of CFR due to a decrease of coronary flow velocity at rest and its more pronounced hyperemic rise was found in all patients after stent implantation (CFR: 1.28+/-0.52 before and 2.53+/-0.37 after stenting; p<0.001). Using a cut-off value of CFR more or equal 2.0 to identify absence of significant coronary artery disease, TTE detected successful stent implantation with a sensitivity of 91.7% and specificity of 100% for both LAD and RCA. CFR was still abnormal in only 1 patient with pre-procedure>90% LAD stenosis. TTE is a feasible technique for serial CFR evaluation in LAD and PDA. Cut-off CFR value more or equal 2.0 is a sensitive and specific criterion of successful stent implantation in LAD and RCA.

Effect of cardiac resynchronisation therapy on coronary blood flow in patients with non-ischaemic dilated cardiomyopathy

Cardiac resynchronisation therapy (CRT) has beneficial effects on cardiac function, exercise tolerance, symptoms, and prognosis. Coronary blood flow impairment has been observed in patients with non-ischaemic dilated cardiomyopathy (DCM) despite angiographically normal coronary arteries. No data are available on coronary blood flow and coronary flow reserve (CFR) measured by intracoronary Doppler in different coronary arteries in patients with DCM and left bundle branch block (LBBB) before and during treatment with CRT. Thus, the major aim of our study was to assess the effect of CRT on coronary blood flow in patients with non-ischaemic DCM and to compare coronary blood flow and CFR measured in the 3 major coronary arteries (left anterior descending [LAD], left circumflex [LCX], and right coronary artery [RCA]). Twenty one patients with DCM and LBBB (mean left ventricular ejection fraction 26 ± 7%, 5 females, mean age 57.8 ± 8.1 years) were studied. Average peak velocity, diastolic/systolic velocity ratio and CFR were measured using intracoronary Doppler before and 6-9 months after implantation of CRT-D or CRT-P. In patients with a clinical improvement (71.4%), CFR increased in LAD. CFR measured in LCX and RCA did not improve either in the overall study group or in patients with a clinical improvement. The observed increase in CFR in LAD correlated only with reduction of QRS duration. In non-ischaemic DCM, CFR is reduced only in LAD. A significant improvement of CFR in LAD after CRT correlates with reduction of QRS duration.

Association between Cardiac Troponin Level and Coronary Flow Reserve in Patients without Coronary Artery Disease: Insight from a Thermodilution Technique Using an Intracoronary Pressure Wire.

Background and ObjectivesCardiac troponins are associated with increased mortality, even among patients with no coronary artery disease. Elevated cardiac troponin levels are frequently observed in patients without significant coronary lesions, although the mechanism underlying this finding is unclear. The aim of our study was to evaluate the association between the levels of cardiac troponin and coronary flow reserve (CFR).Subjects and MethodsWe evaluated serum cardiac troponin-I in 19 patients (9 female; age 61.9±10.9 year-old). All patients had an ejection fraction >40% and angiographically normal coronary arteries. Simultaneous measurements of fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and CFR measurements using an intracoronary temperature- and pressure-sensing guidewire under basal conditions and during maximal hyperemia were performed in three vessels: the left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA).ResultsAll patients were followed for a median of 13 months. FFR, IMR, and CFR measurements were performed successfully in all subjects. Mean CFRs of LAD, LCX, and RCA were 1.98±1.20, 2.75±2.11, and 4.44±2.51, respectively. Mean IMRs of LAD, LCX and RCA were 33.28±18.78, 29.11±26.70, and 30.55±23.65, respectively. There was a poor correlation between CFR and troponin-I values in each vessel. In selecting the lowest value of CFR in each patient as the corresponding value, the lowest CFR was not associated with troponin-I levels (r=-0.219, p=0.367).ConclusionIn patients without significant coronary lesions, the correlation between CFR and troponin-I level was not significant using a thermodilution technique. Further study of a larger population with longer-term follow-up may be needed to more fully understand microvascular dysfunction.

Abstract 8851: Intracoronary Infusion of Cardiosphere-Derived Cells (icCDCs) Improves Cardiac Function by Stimulating Myocyte Proliferation in Non-Infarcted Hibernating Myocardium with No Effect in Normal Myocardium

Background: icCDCs have been shown to improve function and reduce fibrotic area when regionally infused into infarcted myocardium. Their ability to improve flow and function in viable dysfunctional myocardium in the absence of scar is unclear. Methods: Swine (n=12) with collateral-dependent hibernating myocardium from a chronic LAD occlusion were studied 4-months after instrumentation in the closed-chest propofol sedated state. CDCs were isolated from myocardial biopsies at the time of initial instrumentation. We assessed regional flow, LAD wall thickening (%LADWT) and global EF before and 4 weeks after icCDCs (∼40x10 6 cells) into each of the 3 major coronary arteries. Autologous (n=3) as well as non-autologous CDCs with cyclosporine treatment (200mg/day; n=3) had similar effects and results were pooled and compared to untreated swine (n=6). Histological analysis was performed to assess the frequency of Ki-67 and phospho-Histone H3 (pHH3) positive myocytes along with myocyte nuclear density and myocyte diameter. Results: Infusion of icCDCs in normal animals (icCDCs; n=5 vs. untreated; n=6) did not affect regional (%LADWT 51±1% vs. 48±3%, p-ns) or global function (EF: 70±2% vs. 70±3%, p-ns). In contrast, in hibernating myocardium, %LADWT increased from 23±6 to 51±5 % (p&lt;0.01) and EF increased from 57±1 to 71±4 % (p&lt;0.01) after icCDCs. There was no change in LAD coronary flow reserve (adenosine vasodilated flow/ resting flow 1.88 ± 0.20 to 2.03 ± 0.31, p-ns). icCDCs increased the number of Ki-67 and pHH3 positive myocytes (Table). This was accompanied by a prominent increase in myocyte nuclear density with reduced myocyte size suggesting the formation of new myocytes. Conclusion: We conclude that icCDCs result in a robust improvement in function in hibernating myocardium. This is not secondary to increases in myocardial perfusion but is secondary to pronounced myocyte proliferation and regeneration with newly formed myocytes in diseased but not normal myocardium.

Faisabilité et intérêt de la mesure de la réserve coronaire de l’IVA lors de l’échographie dobutamine

Aim of the study To assess the value of the coronary flow reserve (CFR) in the left anterior descending artery (LAD) during dobutamine stress echocardiography in the diagnosis of significant LAD stenosis (more than 70%). Method Retrospective study of 81 patients with a positive stress echocardiography who underwent a coronarography. Results Measurement of coronary flow reserve was able in half echocardiographic exams. Medium Pic diastolic velocity was 0.33 m/s (SD 0.20), medium maximal diastolic velocity during stress was 0.62 m/s (SD 0.20), medium CFR was 2.25 (SD 0.65). In 50 patients LAD was not seen; in five of them LAD was occluded. The predictive positive value (PPV) of a low coronary flow reserve to detect LAD stenosis is 66.7% and the negative predictive value (NPV) is 65.4%. An abnormal anterior contraction during stress echo with a low reserve has a PPV of 75% for the diagnosis of significant IVA stenosis and a normal contraction during stress with normal coronary flow reserve means a NPV of 65%. We did not show a significant correlation between low coronary flow and abnormal contraction during stress echocardiography (kappa 0.51). Conclusion Coronary flow reserve of LAD during stress echo is feasible but does not really improve exam performance to detect significant IVA stenosis. This measurement remains to be clear in coronary patients management.

Prognostic Value of Left and Right Coronary Flow Reserve Assessment in Nonischemic Dilated Cardiomyopathy by Transthoracic Doppler Echocardiography

Background Coronary flow reserve (CFR) in the left anterior descending artery (LAD) can be reduced in nonischemic dilated cardiomyopathy (DCM). The aim of this study was to assess the prognostic value of CFR in LAD and in the posterior descending artery (PD) in DCM patients. Methods Seventy-two DCM patients (44 men, mean age 64 ± 13 years) underwent dipyridamole (0.84 mg/kg in 6 minutes) stress echo. CFR was defined as the ratio between maximal vasodilation and rest peak diastolic flow velocity in LAD and PD. Results CFR was abnormal in LAD in 42 out of 72 patients and in PD in 31 out of 55. All patients completed the clinical follow-up, and 56 patients completed the echocardiographic follow-up. During median follow-up of 42 months, 33 events (7 deaths, 26 major cardiac events) occurred. Event rate was markedly higher for patients with reduced CFR compared with DCM patients with normal CRF in LAD (0 vs 19 events; P < .001) and in PD (1 vs 13 events; P < .001). CFR in LAD and in PD were significantly related to the change in end-systolic volume during follow-up ( r = −0.481, P < .001; and r = −0.407, P = .028; respectively). Preserved CFR in both LAD and PD was associated with better ( P < .0001) event-free survival compared with abnormal CFR (log rank: 28.1; P < .0001). Conclusions In DCM patients, impairment of CFR in LAD and PD is related to a worse outcome; CFR impairment is more relevant when it occurs in LAD. PD evaluation may be redundant and time-consuming, because the additive value is small and the feasibility suboptimal.

Recovery of distal coronary flow reserve in LAD and LCx after Y-Graft intervention assessed by transthoracic echocardiography

BackgroundY- graft (Y-G) is a graft formed by the Left Internal Mammary Artery (LIMA) connected to the Left Anterior Descending Artery (LAD) and by a free Right Internal Mammary Artery (RIMA) connected to LIMA and to a Marginal artery of Left Circumflex Artery (LCx). Aim of the work was to study the flow of this graft during a six months follow-up to assess whether the graft was able to meet the request of all the left coronary circulation, and to assess whether it could be done by evaluation of coronary flow reserve (CFR).MethodsIn 13 consecutive patients submitted to Y-G (13 men), CFR was measured in distal LAD and in distal LCx from 1 week after , every two months, up to six months after operation (a total of 8 tests for each patient) by means of transthoracic echocardiography (TTE) and Adenosine infusion (140 mcg/kg/min for 3-6 min). A Sequoia 256, Acuson-Siemens, was used. Contrast was used when necessary (Levovist 300 mg/ml solution at a rate of 0,5-1 ml/min). Max coronary flow diastolic velocity post-/pre-test ≥2 was considered normal CFR.ResultsCoronary arteriography revealed patency of both branches of Y-G after six months. Accuracy of TTE was 100% for LAD and 85% for LCx. Feasibility was 100% for LAD and 85% for LCx. CFR improved from baseline in LAD (2.21 ± 0.5 to 2.6 ± 0.5, p = 0.03) and in LCx (1.7 ± 1 to 2.12 ± 1, p = 0.05). CFR was under normal at baseline in 30% of patients vs 8% after six months in LAD (p = 0.027), and in 69% of patients vs 30% after six months in LCx (p = 0.066).ConclusionCFR in Y-G is sometimes reduced in both left territories postoperatively but it improves at six months follow-up. A follow-up can be done non-invasively by TTE and CFR evaluation.

Implication of the Continuous Prognostic Spectrum of Doppler Echocardiographic Derived Coronary Flow Reserve on Left Anterior Descending Artery

The additive prognostic value of coronary flow reserve (CFR) over regional wall motion has been established, but there is more than a binary (normal-abnormal) response in CFR, which can be continuously titrated. We assessed the prognostic value of quartiles of CFR, evaluated by transthoracic Doppler of the left anterior descending coronary artery (LAD), in patients with known or suspected coronary artery disease (CAD). One thousand six hundred twenty patients (1,006 men, 64 +/- 11 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with CFR evaluation of LAD by Doppler and coronary angiography. Patients were followed up for a median of 19 months. Mean CFR in the entire population was 2.25 +/- 0.65. Stress echocardiogram was positive for ischemia in 480 patients (30%). Obstructive (>or=70% vessel stenosis) CAD at angiography was present in 650 patients (40%). During follow-up, there were 298 events (42 deaths, 73 ST-elevation myocardial infarctions, and 183 non-ST-elevation myocardial infarctions). Patients (n = 399) undergoing revascularization were censored. With the Kaplan-Meier method, the first quartile of CFR (<or=1.80) was associated with a worse (p <0.0001) event rate than other quartiles in the entire population and in patients with no ischemia at stress echocardiography. Furthermore, the second quartile of CFR (1.81 to 2.16) was predictive of increased (p <0.0001) risk compared to the higher quartiles. In conclusion, Doppler echocardiographically derived CFR in LAD is a strong and independent prognostic predictor in patients with known or suspected CAD, but the spectrum of prognostic stratifications is expanded if the response is titrated according to a continuous scale rather than artificially dichotomized.

Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes

The aim of this study was to validate a new method to measure regional myocardial perfusion reserve (MPR) with technetium-labelled tracers in patients with type 2 diabetes mellitus (DM2). A total of 40 consecutive DM2 patients without history of coronary artery disease (CAD) and 7 control subjects were recruited. Dipyridamole myocardial blood flow index (MBF) was assessed by measuring first transit counts in the pulmonary artery and myocardial count rate from gated SPECT images using (99m)Tc-labelled tracers. The corresponding MBF index was estimated 2 h later according to the same procedure. Regional myocardial perfusion reserve (MPR) was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular (LV) model. Coronary flow reserve (CFR) was estimated by transthoracic contrast echo Doppler monitoring of flow velocity in the left anterior descending coronary artery (LAD) during the same session. Estimated MPR was higher in control subjects than in patients (3.36 +/- 0.66 vs 1.91 +/- 0.61, respectively, p < 0.01). In patients, LAD CFR and LAD MPR were 2.01 +/- 0.78 vs 1.93 +/- 0.63, respectively (p = ns). The agreement between the two techniques was documented by their close correlation (r = 0.92, p < 0.001) and confirmed by the Bland-Altman analysis. Reversible perfusion defects occurred in 13 patients (32%) who showed similar MPR values as the remaining 27 (2.10 +/- 0.71 vs 1.83 +/- 0.71, respectively, p = ns). Finally, MPR was closely correlated with age (r = -0.50, p < 0.01) and time elapsed from the diagnosis of DM2 (r = -0.51, p < 0.01). LV regional MPR can be accurately estimated with the broadly available single photon technology. Application of this method to DM2 patients documents the presence of a microvascular dysfunction homogeneously distributed throughout the LV walls and most frequently not associated with reversible perfusion defects.

Clinical Outcome in Patients with Intermediate Stenosis of Left Anterior Descending Coronary Artery after Deferral of Revascularization on the Basis of Noninvasive Coronary Flow Reserve Measurement

Several reports suggest that noninvasive measurements of coronary flow reserve (CFR) by use of echocardiography may support decision making in intermediate stenosis of the left anterior descending coronary artery (LAD). The aim of the present study was therefore to analyze the clinical outcome in patients with intermediate stenosis of LAD after deferral of coronary revascularization on the basis of noninvasive CFR measurement. the study population included 280 patients with intermediate LAD stenosis (50-70% by angiography) (62.2 +/- 9.6 years). All the patients underwent transthoracic CFR assessment of LAD (after dipyridamole infusion) within 2 weeks from coronary angiography. If CFR of LAD was < or = 2, PTCA was recommended; if CFR was > 2, medical treatment was chosen. Primary end points were cardiac death, myocardial infarction, coronary revascularization procedure, and unstable angina. mean follow-up was 43 +/- 11 months (range 12-52 months). In 150 patients (53.6%) (CFR < or = 2), coronary artery revascularization was performed (PTCA group); the remaining 130 patients (46.4%) (CFR > 2) were medically treated (medical group). Survival from cardiac death was 94% in the PTCA group and 92.4% in the medical group (P = 0.56). As for all cardiac events, the Kaplan-Meier percentage survival from cardiac events was 88.3% in the PTCA group and 86.4% in the medical group (P = 0.36). even if CFR as a "stand-alone" diagnostic criterion suffers from several structural limitations, a combined strategy including also other clinical and instrumental measurements before undergoing interventional procedures could improve the cost-benefit practice, in particular, for the management of patients with intermediate LAD stenosis.

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.

211 Dobutamine stress echo: concordance between wall motion assessment and non-invasively evaluated coronary flow reserve

Aim: To assess consistency between left ventricular (LV) wall motion modification and coronary flow reserve in the left anterior descending coronary artery (LAD) territory during dobutamine stress-echo (DSE). Methods: 173 patients underwent DSE, according to the standard protocol, for evaluation of known or suspected coronary artery disease and, during the test, LAD flow velocity was measured at baseline and at peak stress. Segmental kinesis was evaluated both for all LV segments then limited to LAD territory (aWMSI). Coronary flow reserve (CFR) was calculated as the ratio between peak stress and baseline maximal diastolic velocity in the distal LAD. In a subgroup of 48 patients, without anterior myocardial infarction (MI), accuracy of non-invasively evaluated RFC was verified with coronary angiography data. Results: Patients were predominantly males (122.71%), mean age was 68±11 years; 69% were hypertensive, 37% diabetics, 46% presented dyslipidemia and 53% were smokers. Fifty-two patients had a recent or previous anterior MI, in 30 treated with primary PCI. Baseline echocardiography showed normal LV internal dimensions (end-diastolic volume index 63±20 ml/m 2 ; endsystolic volume index 34±18 ml/mq), with slightly reduced LV global systolic function (ejection fraction 47±27%). During ESD, both global WMSI then aWMSI resulted significantly and negatively correlated with RFC at baseline, after low dose and high dose dobutamine infusion; a similar correlation was also present between RFC and WMSI changes during high dose infusion, indicating extension of inducible ischemia. After exclusion of patients with anterior MI, these correlations remained significant; in the group with anterior MI, CFR was significantly and negatively correlated only with aWMSI after high dose infusion. Considering the final results of DSE and dividing patients in no or mild ischemia and extensive inducible ischemia (more than three LV segments), there was a significant difference in CFR value between the two groups (1.82 vs 2.26, p<0.001); otherwise presence or absence of viability didn’t influence CFR value. In absence of anterior MI, there was a good agreement between coronary angiography and noninvasively evaluated CFR (1.6 in patients with critical LAD stenosis vs 2.2 in patients with non critical lesions, p<0.05). Conclusion: LAD CFR evaluated during DSE demonstrates a good agreement with both LV segmental kinesis and coronary angiographic data, thus offering an adjunctive tool to improve DSE diagnostic accuracy.

Evaluation of Left Anterior Descending Coronary Artery Stenosis of Intermediate Severity Using Transthoracic Coronary Flow Reserve and Dobutamine Stress Echocardiography

The physiologic significance of left anterior descending coronary artery (LAD) stenosis of intermediate angiographic severity is of clinical importance and difficult to assess. Assessment of coronary flow reserve (CFR) by Doppler transthoracic echocardiography (TTE) is a new tool and could allow rapid, noninvasive evaluation of stenosis severity in this setting. We sought to evaluate the value of CFR measurement determined by TTE, compared with dobutamine stress echocardiography (DSE), in the setting of LAD stenosis of intermediate angiographic severity. A total of 51 consecutive stable patients in sinus rhythm (33 men; age 65 +/- 12 years; left ventricular ejection fraction 59 +/- 7%) with no previous anterior myocardial infarction and with an angiographic proximal LAD stenosis of intermediate severity (56 +/- 8% quantitative coronary angioplasty) were prospectively studied. Coronary flow velocity was measured in the distal part of the LAD by TTE at rest and during continuous infusion of 0.14 mg/kg/min of adenosine over 2 minutes, using a multifrequency transducer, in the modified parasternal or 3-apical view. CFR was calculated as the ratio of hyperemic to basal mean (mean CFR) and peak (peak CFR) diastolic flow velocity. DSE was performed immediately after the adenosine test to assess ischemia in the LAD territory (percent maximum predicted heart rate = 94 +/- 8). Adequate recording of CFR was possible in 46 patients. Of the 35 patients with a CFR of 2 or more (peak CFR = 2.7 +/- 0.6), DSE was normal in 34. Of the 11 patients with a CFR less than 2 (peak CFR = 1.7 +/- 0.2), 7 had an abnormal response with DSE in the LAD territory. In this range of intermediate stenosis, there was a poor correlation between percent LAD diameter stenosis and CFR. For patients with positive DSE, CFR was 1.6 +/- 0.2 compared with 2.7 +/- 0.6 for patients with normal DSE (P < .05). The sensitivity, specificity, and the positive and negative predictive values of TTE CFR for detecting ischemia on DSE were 88%, 89%, 64%, and 97%, respectively, with an overall agreement of 89% between the two tests. Given its high negative predictive value, noninvasive CFR could be a useful aid in reaching clinical decisions promptly at the bedside in patients with moderately severe lesions of the proximal LAD.

Transthoracic coronary flow reserve and dobutamine derived myocardial function: a 6-month evaluation after successful coronary angioplasty

After percutaneous transluminal coronary angioplasty (PTCA), stress-echocardiography and gated single photon emission computerized tomography (g-SPECT) are usually performed but both tools have technical limitations. The present study evaluated results of PTCA of left anterior descending artery (LAD) six months after PTCA, by combining transthoracic Doppler coronary flow reserve (CFR) and color Tissue Doppler (C-TD) dobutamine stress.Six months after PTCA of LAD, 24 men, free of angiographic evidence of restenosis, underwent standard Doppler-echocardiography, transthoracic CFR of distal LAD (hyperemic to basal diastolic coronary flow ratio) and C-TD at rest and during dobutamine stress to quantify myocardial systolic (Sm) and diastolic (Em and Am, Em/Am ratio) peak velocities in middle posterior septum. Patients with myocardial infarction, coronary stenosis of non-LAD territory and heart failure were excluded. According to dipyridamole g-SPECT, 13 patients had normal perfusion and 11 with perfusion defects. The 2 groups were comparable for age, wall motion score index (WMSI) and C-TD at rest. However, patients with perfusion defects had lower CFR (2.11 ± 0.4 versus 2.87 ± 0.6, p < 0.002) and septal Sm at high-dose dobutamine (p < 0.01), with higher WMSI (p < 0.05) and stress-echo positivity of LAD territory in 5/11 patients. In the overall population, CFR was related negatively to high-dobutamine WMSI (r = -0.50, p < 0.01) and positively to high-dobutamine Sm of middle septum (r = 0.55, p < 0.005).In conclusion, even in absence of epicardial coronary restenosis, stress perfusion imaging reflects a physiologic impairment in coronary microcirculation function whose magnitude is associated with the degree of regional functional impairment detectable by C-TD.