Value Of Coronary Flow Velocity Reserve Research Articles

Prognostic significance of coronary flow velocity reserve in patients with peripheral arterial disease

Abstract Background Patients with lower extremity peripheral arterial disease (PAD) have a higher risk of cardiovascular events. Stress echocardiography (SE) based on regional wall motion abnormality (RWMA) is imperfect for risk stratification in PAD, but it can be complemented with an assessment of coronary flow velocity reserve (CFVR) in the mid-distal left anterior descending coronary artery. Purpose To assess the value of SE with RWMA and CFVR to predict survival in PAD. Methods In a retrospective analysis of prospectively acquired data in an observational, multicenter study, we recruited 359 patients (age 69±8 years, 240 [67%] males) with PAD referred for dipyridamole SE in 3 accredited laboratories. We assessed RWMA and CFVR (abnormal value <2.0). All patients were followed up for a median of 4.7 (interquartile range: 2.0 to 8.2 years). All-cause death was the outcome end-point. Results The positivity rate was 37/359 (10%) for RWMA and 159/359 (44%) for CFVR. During follow-up, 97 (27%) deaths were registered. At multivariable analysis, inducible RWMA and/or CFVR <2.0 (HR 2.58, 95% CI 1.65-4.04; p<0.0001), age ≥70 years, diabetes, dialysis treatment, and ejection fraction ≤50% were associated with decreased survival. The annual mortality was 7.4% in patients with RWMA and/or CFVR <2.0 and 2.7% in those with no RWMA and CFVR >2.0 (Figure, p<0.0001). Conclusion In patients with PAD, SE shows more than 4-fold higher prevalence of abnormal CFVR compared to RWMA. The prognostic value of CFVR outperforms RWMA, showing the importance of coronary microvascular dysfunction and diffuse, subcritical coronary atherosclerosis in determining the outcome.

Combined Assessment of Fractional Flow Reserve and Coronary Flow Velocity Reserve after Drug-Eluting Stent Implantation

Coronary flow velocity reserve (CFVR) can be measured noninvasively using stress transthoracic Doppler echocardiography (S-TDE). The prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to investigate the prognostic value of post-PCI CFVR and its additional efficacy to fractional flow reserve (FFR) in patients undergoing elective PCI. A retrospective study was conducted involving 187 consecutive patients with chronic coronary syndrome who underwent elective PCI guided by FFR for the left anterior descending coronary artery. Pre- and post-PCI wire-based FFR and CFVR assessments of the left anterior descending coronary artery using S-TDE were performed in all patients. The association between post-PCI clinical and physiologic parameters and major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, heart failure, and unplanned remote target vessel revascularization, was evaluated. Three-quarters of patients exhibited CFVR increase after PCI, while all patients showed FFR improvement. During a median follow-up period of 1.5years, MACE occurred in 21 patients (11.2%). Among clinical demographics, patients with MACE had higher levels of N-terminal pro-brain natriuretic peptide compared with those without MACE (median, 615pg/mL [interquartile range, 245-1,500pg/mL] vs 180pg/mL [interquartile range, 70-559pg/mL]; P=.010). Post-PCI S-TDE-derived CFVR was lower in patients with MACE, while post-PCI FFR showed a nonsignificant tendency to be lower in patients with MACE. In a multivariable analysis, higher NT-proBNP (adjusted hazard ratio, 1.33; 95% CI, 1.02-1.74; P=.038), post-PCI CFVR ≤ 2.0 (adjusted hazard ratio, 2.93; 95% CI, 1.16-7.40; P=.023), and post-PCI FFR ≤ 0.82 (adjusted hazard ratio, 3.93; 95% CI, 1.52-10.18; P=.005) were independently associated with MACE. In patients with chronic coronary syndrome who underwent successful elective PCI for left anterior descending coronary artery, the combined assessment of S-TDE-derived post-PCI CFVR and post-PCI FFR provided a significant association with the occurrence of MACE.

The importance of vasodilator stress echocardiography in predicting all-cause mortality and acute heart failure in hypertrophic cardiomyopathy

Abstract Background Reduced coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) during vasodilator stress echocardiography (VSE) is a marker of poor outcome and is associated with higher baseline coronary flow velocity (CFV) in hypertrophic cardiomyopathy (HCM). However, whether resting CFV has additive predictive value to CFVR during VSE in HCM is unknown. Aim To assess the prognostic value of baseline CFV and CFVR during VSE in HCM. Methods 325 adult HCM patients (age=52+15 years, 147 [45%] females) with preserved left ventricular function and no known coronary artery disease who underwent VSE in 6 certified centers between 1999 and 2021 were prospectively analyzed. VSE modality was adenosine (0.14 mg/kg/min in 2', n=232) or dipyridamole (0.84 mg/kg in 6', n=93). CFVR in the LAD was assessed by transthoracic (n=306) or transoesophageal (n=19) echocardiography. Patients were followed for a median of 67 months (IQ range 31-103 months), the primary endpoint was a composite of all-cause mortality and acute heart failure (HF). Results Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (>31 cm/s, elevated) and CFVR (≤2.0, reduced) to predict the primary endpoint. Patients with reduced CFVR had more frequently elevated baseline CFV (75% vs 49%, p<0.001). Elevated resting CFV was a predictor of composite endpoint at univariable (HR 2.04, 95% CI 11.05-3.97, p=0.035) but not at multivariable analysis. A reduced CFVR was an independent predictor of all-cause mortality (HR 5.50, 95% CI 1.94-15.59, p=0.001), acute HF (HR 5.80, 95% CI 1.60-21.00, p=0.007), and the composite end-point (HR 4.95, 95% CI 2.39-10.25, p<0.001). The 5-year event rate was 6-fold higher in patients with reduced CFVR compared to patients with preserved CFVR (19% vs 3%, p<0.001), with no additional impact of resting CFV (see Figure). Conclusion LAD CFVR ≤2.0 during VSE is a strong and independent predictor of all-cause mortality and acute HF in HCM. Elevated resting CFV is more frequent in patients with reduced CFVR, but has no independent prognostic value when CFVR is considered.Kaplan-Meier event-free survival curves

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging.

Background: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. Purpose: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. Methods: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27–74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10–40 μg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. Results: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967–1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001–0.534; p = 0.019; OR: 1.147; 95% CI: 1.042–1.263; p = 0.005; respectively). Conclusions: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.

Comparison of coronary flow reserve feasibility and values in different stress echocardiography protocols: dobutamine, dipyridamole, exercise and rapid pacing

Abstract Background and aims To compare the feasibility of Coronary Flow Velocity Reserve (CFVR) assessment in the left anterior descending (LAD) artery in four types of stress echocardiography (SE): dobutamine (DOB), dipyridamole (DIP), rapid pacing (PAC) and bicycle exercise (EXE). Methods and results We subjected 369 patients (mean age: 67±11 years) to SE with DOB (up to 40 mcg/kg/min, n=230), DIP (0.84 mg/kg, n=73), PAC (n=22) or EXE (n=44). CFVR was measured as the ratio of peak diastolic coronary flow velocity (CFV) during exercise, pharmacological stress or pacing and peak diastolic CFV at rest in distal or mid LAD. The feasibility was excellent during PAC (100%), DOB (95%) and DIP (95%) and lower during EXE (73%, p&amp;lt;0.01 vs other groups) when assessed in all consecutive patients. When assessed in patients having readable LAD flow at rest the feasibility achieved even higher values, being however still lowered in EXE group, see Figure 1. In multivariate analysis only the EXE protocol was a predictor of LAD flow loss during SE, with OR = 8.23 (95% CI 2.17 – 31.33), p=0.0019. CFVR was lower with PAC (1.8±0.4) as compared to DIP (2.2±0.6, p=0.0061) and DOB (2.2±0.6, p=0.0025), but similar to EXE (2.0±0.6, p=0.178), and correlated best with the peak heart rate in EXE and PAC, see Figure 2. Conclusion CFVR in LAD can be obtained during all forms of SE, but the feasibility is significantly higher with PAC and pharmacological tests as compared to EXE, which was identified in our study as the independent predictor of the loss of LAD flow recording at the peak of stress test. Moreover, CFVR values were the lowest in PAC group which however encompassed the older patients with more advanced coronary artery disease. Significant correlation between HR and CFVR observed in EXE and PAC suggests that in this type of SE cut-off value of CFVR should be probably indexed to maximal HR achieved. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Prognostic Value of Transthoracic Doppler Echocardiography Coronary Flow Velocity Reserve in Patients With Asymmetric Hypertrophic Cardiomyopathy.

BackgroundMicrovascular dysfunction might be a major determinant of clinical deterioration and outcome in patients with hypertrophic cardiomyopathy (HCM). However, long‐term prognostic value of transthoracic Doppler echocardiography (TDE) coronary flow velocity reserve (CFVR) on clinical outcome is uncertain in HCM patients. Therefore, the aim of our study was to assess long‐term prognostic value of CFVR on clinical outcome in HCM population.Methods and ResultsWe prospectively included 150 HCM patients (82 women; mean age 48±15 years). Patients’ clinical characteristics, echocardiographic and CFVR findings (both for left anterior descending [LAD] and posterior descending artery [PD]), were assessed in all patients. The primary outcome was a composite of: HCM related death, heart failure requiring hospitalization, sustained ventricular tachycardia and ischemic stroke. Patients were stratified into 2 subgroups depending on CFVR LAD value: Group 1 (CFVR LAD>2, [n=87]) and Group 2 (CFVR LAD≤2, [n=63]). During a median follow‐up of 88 months, 41/150 (27.3%) patients had adverse cardiac events. In Group 1, there were 8/87 (9.2%), whereas in Group 2 there were 33/63 (52.4%, P<0.001 vs. Group 1) adverse cardiac events. By Kaplan‐Meier analysis, patients with preserved CFVR LAD had significantly higher cumulative event‐free survival rate compared to patients with impaired CFVR LAD (96.4% and 90.9% versus 66.9% and 40.0%, at 5 and 8 years, respectively: log‐rank 37.2, P<0.001). Multivariable analysis identified only CFVR LAD≤2 as an independent predictor for adverse cardiac outcome (HR 6.54; 95% CI 2.83–16.30, P<0.001), while CFVR PD was not significantly associated with outcome.ConclusionsIn patients with HCM, impaired CFVR LAD (≤2) is a strong, independent predictor of adverse cardiac outcome. When the aim of testing is HCM risk stratification and CFVR LAD data are available, the evaluation of CFVR PD is redundant.

Cut-off value of coronary flow velocity reserve obtained by transthoracic Doppler echocardiography during intravenous infusion of dobutamine for diagnosis of functional significant myocardial bridging

Abstract Background Recent studies showed that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during inotropic stimulation with dobutamine (DOB), in comparison to vasodilation with adenosine, provides more reliable functional evaluation of myocardial bridging (MB). However, the adequate cut-off value of CFVR during DOB for diagnosing functional significant MB has not been fully established. Purpose The purpose of the study was to evaluate the adequate cut-off value of TTDE- CFVR during DOB for diagnosis of functional significant MB. Methods This prospective study included 79 patients (54 males, mean age 55±10 years) with angiographic evidence of isolated MB on the left anterior descending artery (LAD) and systolic compression ≥50% diameter stenosis. Exercise stress-echocardiography test (ExSE) and TTDE-CFVR in the distal segment of LAD during DOB infusion (DOB: 10–40μg/kg/min) were performed in all patients. Percent diameter stenosis (DS) of MB at end-systole and end-diastole were analyzed using quantitative coronary angiography. Results Exercise-SE was positive for myocardial ischemia in 22/79 (28%). CFVR during peak DOB was significantly lower in SE-positive group in comparison to SE-negative group (1.94±0.16 vs. 2.78±0.53, p&amp;lt;0.001). ROC analysis identifies the optimal CFVR during peak DOB cut-off value &amp;lt;2.1 (AUC 0.985, 95% CI: 0.965–1.000, p&amp;lt;0.001), with a sensitivity of 96% and specificity of 95%, positive predictive value of 88%, and negative predictive value of 98%, for identifying functionally significant MB associated with stress-induced myocardial ischemia. The categorical agreement between TTDE-CFVR at peak DOB and ExSE was high (kappa value = 0.877, p&amp;lt;0.001). Multivariate logistic regression analysis showed that percent DS at end-diastole was the only independent predictor of ischemic CFVR value &amp;lt;2.1 (OR: 1.136, 95% CI: 1.045–1.235, p=0.003). Conclusion A cut-off value &amp;lt;2.1 of CFVR during DOB infusion obtained by TTDE may adequate discriminate functional significant MB that induce myocardial ischemia which is caused by an incomplete diastolic MB-decompression. Funding Acknowledgement Type of funding sources: None.

Prognostic value of coronary flow velocity reserve in patients with homozygous familial hypercholesterolemia.

Coronary flow velocity reserve (CFVR) can provide useful quantitative information on the functional status of coronary artery circulation, and an impaired CFVR (<2.0) was associated with a significant increase in the occurrence of cardiac events. Coronary artery disease (CAD) is the leading cause of death in homozygous familial hypercholesterolemia (HoFH), but the relationship between impaired CFVR and outcome in HoFH has never been discussed before METHODS: To explore the long-term prognostic value of CFVR in patients with HoFH, 39 HoFH patients with CFVR data (mean age with 16.7 years) were enrolled from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. All patients were divided into impaired CFVR (CFVR<2.0, n=17) and preserved CFVR (CFVR≥2.0, n=22) group. Follow-up was performed until a major adverse cardiac event (MACE) occurred or up to June 30, 2020 RESULTS: During a median follow-up of 89 months, 16 events were registered, 12 of which were occurred in the impaired CFVR group and four occurred in the preserved CFVR group. The event-free survival rate of impaired CFVR group was significantly lower than that in the preserved CFVR group (29.4%vs 81.8%, P<.001), and CFVR<2.0 was independently associated with prognosis before and after adjustment for related risk factors (HR 5.197, 95% CI 1.669 to 16.178, P=.004 and HR 5.488, 95% CI 1.470 to 20.496, P=.011, respectively) CONCLUSIONS: an impaired CFVR predicts a worse outcome in HoFH. CFVR shows an independent value in the prediction of long-term outcome in HoFH.

Prognostic role of coronary flow velocity reserve in hypertrophic cardiomyopathy

Abstract Background A reduction in coronary flow velocity reserve (CFVR) related to coronary microvascular dysfunction is a major mechanism for ischemia in hypertrophic cardiomyopathy (HCM). Hypothesis To assess the functional correlates and prognostic value of CFVR during stress echocardiography (SE) in HCM. Methods We enrolled 201 HCM patients (age 51±14 years, 105 male, 52%; maximal wall thickness: 18±3 mm) studied with CFVR during exercise (n=33, 16.4%), dipyridamole (n=89, 44.3%) or adenosine (n=79, 39.3%) SE in 6 certified centers. CFVR was assessed using pulsed wave Doppler sampling in left anterior descending coronary artery. All patients completed the clinical follow-up. Results During SE mean value of CFVR was 2.11±0.46. No patients showed regional wall motion abnormalities during stress. LV outflow tract obstruction (LVOTO) was present in 34 (16.9%) patients at rest and in 47 (23.4%) at peak stress. CFVR was inversely related to age (r=−0.229, p=0.001) and maximal wall thickness (r=−0.197, p=0.031). During a median follow-up of 26 months (IQ range: 12–48 months), 75 events in 63 patients occurred: 10 deaths, 33 new hospital admission for acute heart failure, 8 sustained ventricular tachycardias and 24 atrial fibrillations. Patients in the lowest tertile (≤1.88) showed the worse prognosis with higher incidence of follow-up events compared to median tertile (1.89–2.29) and highest tertile (≥2.30) (see figure). At multivariable analysis, NYHA functional class (HR: 2.234, 95% CI: 1.398–3.517, p=0.001), presence of LVOTO at rest (HR: 2.958, 95% CI: 1.074–3.570, p=0.028) and lowest tertile of CFVR (HR: 2.144, 95% CI: 1.126–4.081, p=0.011) were the independent predictors of follow-up events. Conclusions In HCM patients, reduction in CFVR is associated to a clearly worse outcome. The spectrum of prognostic stratification is expanded if the response is titrated according to a continuous scale. Figure 1 Funding Acknowledgement Type of funding source: None

Impairment of coronary flow velocity reserve and global longitudinal strain in women with cardiac syndrome X and slow coronary flow

BackgroundMicrovascular dysfunction (MVD) is associated with adverse prognosis and may account for abnormal stress tests and angina symptoms in women with cardiac syndrome X (CSX). The aim of our study was to assess MVD by coronary flow velocity reserve (CFVR) and left ventricular (LV) contractile function by LV global longitudinal strain (LVGLS) in CSX patients with respect to presence of slow coronary flow (SCF). It was of additional importance to evaluate clinical status of CSX patients using Seattle Angina Questionnaire. Methods and resultsStudy population included 70 women with CSX (mean age 61 ± 7 years) and 34 age-matched controls. CSX group was stratified into two subgroups depending on SCF presence: CSX-Thrombolysis In Myocardial Infarction (TIMI) 3- normal flow subgroup (n = 38) and CSX-TIMI 2- SCF subgroup (n = 32) as defined by coronary angiography. LVGLS measurements and CFVR of left anterior descending (LAD) and posterior descending (PD) artery were performed. CFVR-LAD and PD were markedly impaired in CSX group compared to controls (2.34 ± 0.25 vs 3.05 ± 0.21, p < 0.001; 2.32 ± 0.24 vs 3.01 ± 0.13, p < 0.001), and furthermore decreased in CSX-TIMI 2 patients. Resting, peak, and ΔLVGLS were all significantly impaired in CSX group compared to controls (for all p < 0.001), and furthermore reduced in CSX-TIMI 2 subgroup. Strongest correlation was found between peak LVGLS and CFVR LAD (r = −0.784, p < 0.001) and PD (r = −0.772, p < 0.001). CSX-TIMI 2 subgroup had more frequent angina symptoms and more impaired quality of life. ConclusionsMVD in CSX patients is demonstrated by reduction in CFVR and LVGLS values. SCF implies more profound impairment of microvascular and LV systolic function along with worse clinical presentation.

Diagnostic accuracy of stress myocardial computed tomography perfusion imaging to detect myocardial ischemia: a comparison with coronary flow velocity reserve derived from transthoracic Doppler echocardiography

BackgroundOur aim was to evaluate the ability of adenosine triphosphate (ATP)-stress myocardial computed tomography perfusion (CTP) imaging to detect myocardial ischemia in the left anterior descending artery (LAD) territory, and to compare this method with coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography (TTDE). MethodsATP-stress CTP and CFVR were performed in 50 patients with stable angina pectoris. Myocardial ischemia assessed from CTP imaging was defined as qualitative visual perfusion defects and reduced myocardial blood flow (MBF) based on quantitative assessment. A cut-off value of CFVR of 2.0 was used. ResultsThe mean CFVR was 1.9 ± 0.6 in ischemic regions by CTP, whereas it was 2.9 ± 0.8 in non-ischemic regions (p < 0.001). CTP imaging could accurately predict CFVR <2.0 with 84.0% diagnostic accuracy (94.7% sensitivity, 77.4% specificity, 72.0% positive predictive value, and 96.0% negative predictive value). When receiver operating characteristic curve analysis of the MBF data was performed to detect CFVR <2.0, the area under the curve was 0.89, and the optimal MBF cut-off value was 1.43 mL/g/min. ConclusionsThis study suggests that qualitative and quantitative assessment of ATP-stress CTP exhibits a good correlation with CFVR for evaluation of myocardial ischemia.

Coronary Flow Velocity Reserve Reduction Is Associated with Cardiovascular, Cancer, and Noncancer, Noncardiovascular Mortality

Coronary flow velocity reserve (CFVR) measured in the left anterior descending artery during high-dose vasodilator stress echocardiography interrogates both epicardial and microcirculatory coronary function and has been inversely associated with chronic inflammation and microvascular dysfunction, as well as with the presence of obstructive coronary artery disease. Microvascular dysfunction and chronic inflammation are common mechanisms of disease in cardiovascular (CV) and non-CV conditions. We aimed to assess whether CFVR is associated with all-cause death, but more specifically with CV, cancer, and non-CV and noncancer (NCVNC) mortality, independently and increasingly over other demographic, clinical, and echocardiography variables. One thousand two patients who underwent stress echocardiography were followed for a median of 8.2years, with clinical, regional wall motion abnormalities (RWMAs), and CFVR data. The independent prognostic value of RWMA and CFVR regarding CV, cancer, or NCVNC mortality was evaluated adjusting for clinical variables. A prespecified subgroup of subjects with no RWMA or revascularization procedures during follow-up was also analyzed (n=752), to exclude most participants with possible coronary artery disease and remove such confounding from the assessment of the potential association of CFVR and mortality. A total of 161 patients (16%) died, 63 deaths being CV (39%), 52 from cancer (32%), and 46 (29%) from NCVNC causes. In comparison to CV mortality, cancer and NCVNC mortality were not associated with an ischemic RWMA at univariable analysis, while a CFVR < 2 was significantly associated with each category of cause-specific mortality. A CFVR < 2 or ≥2 separated a group of patients with 8-year 14.6% versus 1.2% CV mortality, 10.3% versus 0.4% cancer mortality, and 9.5% versus 1.5% NCVNC mortality. The reduction of CFVR is independently associated with CV, cancer, and NCVNC death in a population clinically referred for suspected/known coronary artery disease. CFVR can act as a marker or a mechanism preceding and predicting mortality from a wide variety of diseases.

Platelet aggregation and response to aspirin therapy in cardiac allograft vasculopathy

Long-term survival after heart transplantation (HTx) is compromised by cardiac allograft vasculopathy (CAV) characterized by coronary macro- and microvascular disease. The pathogenesis of CAV is unclear and may involve coronary thrombosis. We investigated whether HTx patients with CAV had higher platelet aggregation and turnover than HTx patients without CAV and healthy controls. Furthermore, we investigated the anti-platelet effect of low-dose aspirin in HTx patients. We included 57 patients who had undergone HTx (median 8.3 years from HTx) and 57 healthy controls. Platelet aggregation was measured on-aspirin and off-aspirin using impedance aggregometry with adenosine diphosphate (ADP) and arachidonic acid (AA). We evaluated platelet turnover by flow cytometry, CAV burden by coronary angiography and echocardiography, and microvascular function by echocardiographic coronary flow velocity reserve (CFVR). Off-aspirin, HTx patients with CAV (n = 21) had higher ADP-induced platelet aggregation than healthy controls (p < 0.01) and HTx patients without CAV (n = 36) (p < 0.05). Aspirin treatment reduced AA-induced platelet aggregation in both HTx groups, but HTx patients with CAV had higher platelet aggregation on-aspirin than HTx patients without CAV (p < 0.05). Platelet turnover did not differ between HTx patients with CAV and HTx patients without CAV (p > 0.34). HTx patients with lower CFVR values had higher platelet aggregation than HTx patients with higher CFVR values (p < 0.05). Off-aspirin, platelet aggregation was higher in HTx patients with CAV than in HTx patients without CAV and healthy controls. On-aspirin, platelet aggregation was higher in HTx patients with CAV than in HTx patients without CAV. Aspirin monotherapy may not provide sufficient platelet inhibition in HTx patients with CAV.

P1792 Coronary flow velocity reserve and prognosis during stress echocardiography

Abstract OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background Stress echocardiography (SE) based on regional wall motion abnormalities (RWMA) has established risk stratification capabilities, further enhanced by assessment of coronary flow velocity reserve (CFVR) on mid-distal left anterior descending coronary artery which assesses not only epicardial coronary artery stenosis but also coronary microcirculation. Aim To assess the value of CFVR in predicting outcome Methods From September 2016 to December 2018, we enrolled 1848 patients (age 63 ± 11 years; 1121 males, 60%) with known or suspected coronary artery disease and/or heart failure evaluated with SE (exercise in 631, dipyridamole in 1184, adenosine in 10, dobutamine in 43) in 9 quality-controlled centers of 6 countries. CFVR was measured from pulsed wave Doppler as peak/rest ratio of peak diastolic flow. All patients were followed-up for a median of 16 months. Results CFV was 28 ± 10 cm/s at rest and 62 ± 19 cm/s at peak stress (p&amp;lt;.001) with a CFVR of 2.25 ± 0.58. At individual patient analysis, CFVR was abnormal (≤2.0) in 528 (28%) patients: 265 (42%) with exercise, 254 (21%) with vasodilator and 9 (21%) with dobutamine stress. At follow-up, there were 218 events: 22 deaths, 22 non-fatal myocardial infarctions, 62 acute heart failures, and 112 late (&amp;gt; 3 months from SE) myocardial revascularizations. At multivariable analysis, stress-induced RWMA (Hazard Ratio 3.883, 95% Confidence Intervals: 2.379-6.336, p&amp;lt;.0.001) and CFVR (Hazard Ratio 1.590, 95% Confidence Intervals: 1.123-2.275, p&amp;lt;.009) were independent predictors. Kaplan-Meier curves showed progressively worsening event-free survival with progressively lower values of CFVR: see figure Conclusion In patients referred to SE, CFVR assessing coronary microvascular dysfunction allows a more accurate prediction of outcome than RWMA which only detect epicardial coronary artery stenoses. Abstract P1792 Figure. CFVR and event-free survival curves

P1401 The prognostic value of the reduction of coronary flow velocity reserve in non-ischemic heart failure patients

Abstract OnBehalf Stress Echo 2020 study group of the Italian Society of Cardiovascular Imaging Background Coronary microvascular abnormalities determining a reduction of coronary flow velocity reserve (CFVR) have been described in patients (pts) with non-ischemic heart failure (HF). Aim To assess the prognostic value of CFVR in HF. Methods In a prospective, observational, multicenter study, we recruited 333 pts with angiographically normal coronary arteries: 105 patients with HF and preserved (&amp;gt;50%) ejection fraction (HFpEF); 71 with HF and mid-range (40-50%) ejection fraction (HFmrEF); 157 with HF and reduced (&amp;lt;40%) ejection fraction (HFrEF). All patients underwent vasodilator SE with dipyridamole (0.84 mg/kg) in 10 accredited laboratories of 5 countries (Argentina, Brazil, Italy, Mexico, Serbia). CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed wave-Doppler assessment of LAD flow. In all patients we also assessed left ventricular contractile reserve (LVCR) based on force (systolic blood pressure/end-systolic volume) Abnormal cutoff values were ≤2.0 for CFVR and ≤1.1 for LVCR. All pts were followed-up. Results After a median follow-up time of 15 months, 78 events occurred: 36 hospital admissions for acute decompensated heart failure, 23 deaths, 16 worsening in NYHA functional class, 2 stroke and 1 late revascularization. Event-free survival was best in patients with preserved CFVR and LVCR and worst in pts with reduced CFVR and impaired LVCR, with intermediate values for patients with either one (CFVR or LVCR) abnormal results: see figure. A preserved CFVR was associated with a better 24-month event-free survival than reduced CFVR in a subset analysis in pts with HFpEF (HR = 16.2, 95% CI, 1.8-145.1, p = 0.001) and in HFrEF (HR = 3.06, 95% CI, 1.6-5.6, p &amp;lt; 0.001). A multivariable analysis in the overall group of HF pts identified a reduced CFVR as the only independent predictor of event-free survival (HR = 3.455,95% CI 1.723-6.929). Conclusions A reduction in CFVR identifies a high risk subset in HF patients, outlining a shared role of coronary microvascular abnormalities as a marker and potential therapeutic target of HF, independently of underlying EF. Abstract P1401 Figure. Event-free survival based on CFVR-LVCR

Age- and Gender-Specific Prognostic Cutoff Values of Coronary Flow Velocity Reserve in Vasodilator Stress Echocardiography

Coronary flow velocity reserve (CFVR) of the left anterior descending artery is useful for risk stratification during stress echocardiography (SE) as an add-on to regional wall motion abnormalities (RWMA). We sought to provide sex- and age-specific prognostic cutoff values for CFVR. A total of 5,577 patients (2,284 women; 110 age≥85years) who underwent dipyridamole SE with evaluation of RWMA and CFVR were enrolled in a multicenter prospective SE registry. Death and myocardial infarction were the clinical end points. During 20months' median follow-up, 649 events (236 deaths, 413 infarctions) occurred: 288 in women and 38 in patients ≥85years. At receiver operating characteristics analysis, the best prognostic cutoff value for CFVR was similar for men (2.03) and women (2.02) and consistent across all age strata (<45years: 2.03; 45-54years: 2.04; 45-64years: 2.03; 65-74 and 75-84years: 2.0) except for patients >85years, who showed 1.90 as the optimal value. Independent predictors of mortality or myocardial infarction were RWMA (hazard ratio [HR]=5.42), reduced CFVR (HR=3.26), resting ejection fraction (HR=0.98), smoking habit (HR=1.41), age (HR=1.02), and prior percutaneous coronary intervention (HR=1.20) in patients age <85years; and RWMA (HR=5.42), smoking habit (HR=3.24), and resting ejection fraction (HR=0.97) in those age ≥85years. CFVR added a prognostic contribution over clinical parameters, resting ejection fraction, and stress-induced RWMA in all age and sex groups except men >85years. A sex-independent value of CFVR ≤2.0 provides the optimal prognostication across all age groups, except for those ≥85years in whom a cutoff ≤1.90 is needed. Risk stratification is more effective for all age groups when CFVR is combined with RWMA.

Functional assessment of improvement of myocardial ischemia using coronary flow velocity reserve after coronary artery bypass surgery in hemodialysis.

In patients with end-stage renal disease requiring hemodialysis (HD patients), myocardial ischemia after coronary artery disease is a major cause of mortality. Coronary pathophysiology, namely myocardial microvascular dysfunction, appears to differ from patients not requiring HD (non-HD patients). We compared functional improvement of myocardial ischemia after coronary artery bypass surgery (CABG) between HD and non-HD patients by transthoracic coronary flow velocity reserve (CFVR). We retrospectively reviewed isolated CABG patients from between 2008 and 2017. Finally, 161 patients were enrolled; each underwent pre- and postoperative CFVR assessment, and left anterior descending (LAD) artery revascularization with "in-situ" internal mammary artery (IMA). Graft patency was confirmed, and after successful CABG, postoperative CFVR improvement between the two groups was compared. Preoperative CFVR value in group H was 1.81 ± 0.52, group N was 1.93 ± 0.66. There was no significant difference between the groups. IMA to LAD grafts were patent in postoperative evaluation in all patients. Postoperative CFVR in group H was 2.48 ± 0.72 and group N was 2.83 ± 0.73 (P = .042). Significant difference was observed. In both groups, CFVR values improved after successful CABG, but postoperative CFVR values were significant different. In younger populations CFVR values are generally higher. Our HD group was significantly younger than the non-HD group, but CFVR values were postoperatively significantly lower. CFVR values are reportedly affected by both epicardial and microcoronary circulation. In this study population, as all grafts to the LAD were patent, the lower CFVR value in the HD group was considered to have resulted in microvascular disorders.

Coronary reserve in Dobutamine stress echocardiography: Feasibility study and determination of a pathological threshold for myocardial ischemia in the LAD territory

The evaluation of the coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) during a Dobutamine stress echocardiography (DSE) is few realized in current practice. A threshold < 2 would be in favor of myocardial ischemia according to some studies. The main purposes of this study are to analyze the feasibility of the CFVR and to search for a pathological threshold in order to make it a complementary tool in the non-invasive detection for myocardial ischemia in the LAD territory. One hundred and ninety-six consecutive patients referred for detection of myocardial ischemia with contrast-enhanced DSE were evaluated in the GHPSJ from July 2017 to July 2018. CFVR was calculated as a ratio of the distal LAD diastolic peak velocity at rest and peak of stress. The result of the echocardiography was rendered only on the analysis of wall motion abnormalities as a standard reference. The feasibility of CFVR is 94.9%. The pathological threshold of CFVR is ≤ 2.1 (sensitivity of 84.2%, specificity of 70%). The CFVR is altered at 1.87 ± 0.52 in the positive DSE in the LAD territory vs. 2.67 ± 0.91 in the normal ones ( P < 0.001). No significant difference was found between the diabetic and non-diabetic populations ( P = 0.194). The coronary reserve is a non-invasive feasible technique in current practice, sensitive, allowing to add a quantitative criterion to the detection of a myocardial ischemia during a DSE even in non-echogenic patients who needed contrast agent. ( Figure 1 , Cut off value of CFVR).

Prognostic Value of Preserved Coronary Flow Velocity Reserve by Noninvasive Transthoracic Doppler Echocardiography in Patients With Angiographically Intermediate Left Main Stenosis

The potential of angiography to evaluate the hemodynamic severity of a left main coronary artery (LM) stenosis is limited. Noninvasive transthoracic Doppler echocardiographic coronary flow velocity reserve (CFVR) evaluation of intermediate coronary stenosis has demonstrated remarkably high negative prognostic value. The aim of this study was to assess clinical outcomes in patients with angiographically intermediate LM stenosis and preserved CFVR (>2.0) as evaluated by transthoracic Doppler echocardiographic CFVR. The initial study population included 102 patients with intermediate coronary stenosis of the LM referred for transthoracic Doppler echocardiographic CFVR assessment. Peak diastolic CFVR measurements were performed in the distal segment of the left anterior descending coronary artery after intravenous adenosine (140μg/kg/min), and CFVR was calculated as the ratio between maximal hyperemic and baseline coronary flow velocity. Nineteen patients had impaired CFVR (≤2.0) and were excluded from further analysis, as well as two patients with poor acoustic windows. The final group consisted of 81 patients (mean age, 60±9years; 76 men) evaluated for adverse cardiac events including death, myocardial infarction, and revascularization. Mean follow-up duration was 62±26months. Mean CFVR was 2.4±0.4. Total event-free survival was 75 of 81 (92.6%), as six patients were referred for revascularization (five patients with coronary artery bypass grafting, one patient with percutaneous coronary intervention). There were no documented myocardial infarctions or cardiovascular deaths in the follow-up period. In patients with angiographically intermediate and equivocal LM stenosis and preserved CFVR values of >2.0, revascularization can be safely deferred.

Functional Evaluation of the Myocardial Ischemia After Coronary Artery Bypass Surgery Using Coronary Flow Velocity Reserve in Left Ventricular Hypertrophy

Patients with left ventricular hypertrophy (LVH) have reportedly higher than normal mortality and incidences of cardiovascular events. Coronary microvascular pathophysiology also appears to differ from other populations. Such coronary microcirculation dysfunctions are considered strong causes of cardiac events. We compare the functional improvement of myocardial ischemia between LVH patients and other patients after successful coronary artery bypass surgery (CABG) using coronary flow velocity reserve (CFVR) by transthoracic echo cardiography. Patients who underwent isolated coronary artery bypass surgery, including left anterior descending artery (LAD) revascularization via "in situ" internal thoracic artery (ITA) between June 2008 and July 2017 (n = 155), were retrospectively reviewed. ITA grafts were patent in postoperative graft evaluation in all patients. CFVR was evaluated pre- and postoperatively, and data were compared between patients with severe LVH group and those without (non-LVH group). Preoperative mean CFVR was 1.77 ± 0.75 in LVH group and 1.91 ± 0.63 in non-LVH group (P = 0.188). After the operation, ITA to LAD graft patency was confirmed in all patients. Postoperative CFVR was 2.23 ± 0.70 in LVH group and 2.85 ± 0.71 in non-LVH group, respectively (P = 0.002). Significant difference was observed between the 2 groups. CFVR values improved after ITA to LAD bypass grafting in both LVH and non-LVH groups, but postoperative CFVR was significantly lower in patients with severe LVH than in patients without. Myocardial ischemia may exist in patients with LVH, despite patent graft, due to microvascular dysfunction. Comprehensive treatment, including long-term oral medication to improve microvascular dysfunction, is necessary for patients with LVH.