Normal Coronary Flow Reserve Research Articles

Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease.

Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy. 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10-4 M, 81 mcg over 3minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR < 2.5, HMR ≥2, or ≤50% change in coronary blood flow with acetylcholine (CBFACH ). Seventy-two percent had endothelial-dependent epicardial dysfunction (response to ACH: % ∆ in coronary artery diameter and ∆%CBFACH ) and 92% had CMD. Among CMD patients, 65% had CFR < 2.5, 35% had HMR ≥2, and 60% had CBFACH change ≤50%. CFR modestly correlated with HMR (r=-0.38, p < .0001). Among patients with normal CFR, 26% had abnormal epicardial and 20% had abnormal microvascular endothelial dysfunction. Women had a lower CFR (p=.02), higher FFR (p=.03) compared to men. There were no differences in epicardial and microvascular function between patients with stable and unstable angina. In patients with no obstructive CAD: CMD is prevalent, abnormal CFR does not correlate with epicardial or microvascular endothelial dysfunction, women have lower CFR, higher FFR but similar endothelial function compared to men.

Utility of discovery approach using proteomics to create a biomarker profile for coronary microvascular dysfunction

IntroductionCoronary microvascular dysfunction (CMD) is a complex disease, difficult to diagnose and often requires advanced imaging. We used mass spectrometry (MS) using discovery approach to search for serum proteins as potential biomarkers in these patients. MethodsWe used serum samples from 10 patients with CMD and 10 with normal coronary flow reserve (CFR) admitted to an observation unit where acute myocardial infarction was excluded. We identified CMD using 82Rb positron emission tomography/computed tomography as CFR <2 in response to regadenoson, in the absence of coronary calcification or regional perfusion defects. We used MS to identify potential protein biomarkers that were differentially expressed in cases and controls. ResultsBaseline characteristics were not different between cases and controls, except for beta-blocker use and which was higher in cases, and mean (SD) CFR which was lower in cases [1.19 (0.23) and 2.78 (0.78) in cases and controls respectively; p < 0.01]. We identified 5345 peptides corresponding to 209 proteins, and identified 197 proteins by peptides with suitable properties to infer relative quantitation values. While the calculated values for some proteins (e.g. vascular cell adhesion molecule-1, apolipoprotein C and Von Willebrand Factor) indicate fold-differences between groups, these are most likely a result of high values in only 1–2 patients and are not statistically significant. ConclusionMass spectrometry using discovery approach may not be an adequate method for quantitative assessment of serum proteins in CMD patients. Future MS studies should evaluate other approaches including tissue samples or serial measurements.

Reduced Coronary Flow Reserve Is Associated with Impaired Ventricular-vascular Interaction in Patients with Obstructive Sleep Apnea.

Background and ObjectivesObstructive sleep apnea (OSA) is associated with cardiac and arterial damage and adverse cardiovascular outcomes. We aimed to determine whether coronary flow reserve (CFR), which represents microvascular dysfunction, might be associated with the ventricular-vascular coupling index (VVI), which represents the afterload-adjusted contractility in patients with OSA.MethodsWe enrolled 281 patients (257 males; mean age, 43±11 years) with newly diagnosed OSA. Transthoracic echocardiography was performed, and adenosine-associated CFR was measured in the left anterior descending coronary artery. We evaluated the differences between the patients with normal CFR ≥2.5 and reduced CFR <2.5. VVI was calculated using the effective arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees) as follows: 10×Ea/Ees.ResultsThe normal CFR group (n=214) showed increased Ees (7.28±2.31 vs. 8.14±2.33 mmHg/mL, p=0.016) and preserved VVI (3.17±1.53 vs. 2.78±1.20, p=0.044) compared with the reduced CFR group (n=67). There were no differences in LV dimension, LV ejection fraction, left atrial-volume index, E/e′, left atrial strain and LV global longitudinal strain between the 2 groups (all p>0.05). CFR was significantly correlated to Ees (r=0.139; p=0.023) and VVI (r=−0.137; p=0.025).ConclusionsReduced CFR is associated with decreased Ees and impaired VVI in OSA patients. It suggests the necessity of more intensive observation in OSA patients with reduced CFR to improve cardiovascular outcomes.

6115Influence of microvascular function and coronary flow in the diagnostic precision of resting full-cycle ratio

Abstract Introduction Resting full-cycle ratio (RFR) has been recently described as a non-hyperemic index of coronary stenosis with good concordance with Fractional Flow Reserve (FFR). However, there is no information concerning the influence of microvascular function and coronary flow on RFR results. Purpose To determine if the accuracy of this novel parameter might be influenced by changes in microvascular function. Methods 133 patients admitted in our center between July 2016 and December 2017 underwent coronary physiology study of an angiographically intermediate lesion. 67 subjects presented with AMI and an intermediate lesion in a non-culprit artery, and 66 subjects stable coronary disease. We performed FFR, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR) and Resistance Reserve Ratio (RRR) in all of them. We calculated RFR retrospectively from the pressure tracings. Results Coronary physiology parameters showed a non-normal distribution and are presented as median [IQR]: FFR 0.86 [0.79–0.92]; CFR 2.05 [1.4–2.95]; IMR 20.5 [14–32.55]; RRR 2.5 [1.85–3.63]; RFR 0.897 [0.83–0.94]. Patients with abnormal CFR displayed lower RFR values although FFR was not markedly affected (Table 1). These findings remained irrespective of the clinical scenario at presentation. 61 patients had a CFR lower than 2. Correlation between RFR and FFR was not significantly different in patients with abnormal CFR than in those with normal CFR (0,73 vs 0,88; p=0,067) (Figure 1); however, overall binary agreement between RFR and FFR was worse in patients with a low CFR (69% vs 83%; p=0,047). 48 patients had a high IMR (&gt;25). Linear correlation between RFR and FFR was similar in patients with high and normal IMR (0,81 vs 0,83; p=0,784); likewise, binary concordance showed no significant difference between both groups (77% vs 75%, p=0,78). The mean difference between RFR and FFR was 0,025. This was only influenced by CFR: patients with a low CFR had a smaller difference than those with a normal CFR (0,012 vs 0,035; p=0,019). Physiology parameters by CFR group Normal CFR (≥2) Low CFR (&lt;2) P-value FFR 0.88 [0.82–0.93] 0.84 [0.79–0.92] 0.14 RFR 0.91 [0.88–0.95] 0.86 [0.80–0.92] 0.0009 IMR 16.5 [13–27] 25 [16–45.5] 0.002 RRR 3.6 [2.7–4.9] 1.7 [1.3–2.1] &lt;0.0001 Physiological coronary parameters (Median [IQR]) according to CFR. Correlation between RFR and FFR by CFR Conclusion RFR has good overall correlation and concordance with FFR. However, RFR has a lower diagnostic accuracy in patients with a low CFR. Acknowledgement/Funding None

Coronary Flow Reserve Assessment of Orbital Atherectomy: An Observational Pilot Study

The aim of this prospective observational pilot study was to observe the impact of orbital atherectomy (OA) on the coronary microcirculation via coronary flow reserve (CFR) measurements. Fifteen subjects who had successful OA and stent placement with no procedural complication were enrolled at 3 hospitals in the U.S. Baseline and hyperemic velocities were 16 ± 5.2 and 36 ± 14 cm/sec, respectively. The average CFR post-procedure was within the normal range at 2.23 ± 0.33. The observation of normal CFR following OA may be attributed to the orbital action of the device that allows for continuous flow during treatment, minimizing a bolus embolization effect which can impact microvascular function.

Link between von Willebrand factor multimers, relapses and coronary microcirculation in patients with thrombotic thrombocytopenic purpura in remission

IntroductionADAMTS13 deficiency results in unusually large von Willebrand factor (ULVWF) multimers in the circulation and a higher risk of microthrombi due to high shear stress. In patients treated for acquired thrombotic thrombocytopenic purpura (TTP), a persistently severe ADAMTS13 deficiency (<10%) in remission is associated with more relapses. A reduced plasma ADAMTS13 activity and increased VWF levels are associated with a higher risk of myocardial infarction. Assessing coronary flow reserve (CFR) enables a better cardiovascular risk stratification: a lower CFR correlates inversely with cardiovascular risk. The aim of the study was to establish whether patients with TTP in remission have an impaired coronary microcirculation, in terms of a lower CFR, and whether there is any correlation between ADAMTS13 activity, the presence of ULVWF multimers, and the occurrence of relapses. MethodsThe clinical information and hemostatic parameters of 24 patients with TTP in remission managed at our center were analyzed. The CFR was assessed in a subgroup of the TTP patients and compared with a control group consisting of 50 healthy volunteers. ResultsThe CFR was statistically lower in patients in remission of TTP than in controls, but there were no differences between TTP patients with normal and lower CFR. The occurrence of relapses correlated with the presence of ULVWF multimers and with a residual ADAMTS13 activity. ConclusionsWhen compared with healthy controls, TTP patients in remission have an impaired coronary microcirculation and the occurrence of relapses in the former reveal the presence of ULVWF multimers.

(528) - The Clinical Application of Non-Invasive Assessment of Coronary Flow Reserve via Rubidium PET in Heart Transplant Patients

Coronary flow reserve (CFR) has been measured through a flow wire and more recently with the use of nuclear imaging. The advantage of nuclear imaging is that the entire heart is being assessed as opposed to a single coronary artery through the use of the flow wire. Reduction of CFR has implied an abnormal microcirculation in the donor heart due to small vessel transplant coronary artery disease. We have been assessing our patients in a cross-sectional study using Rubidium PET scans to assess CFR. It is not known whether an abnormal CFR (<2.0) is correlated to cardiac function and hemodynamics. Between 2010 and 2014 we assessed 93 heart transplant patients who had undergone Rubidium PET scanning to exclude significant transplant coronary artery disease (TCAD). Patients with abnormal CFR (<2.0) and normal CFR (≥2.0) were compared for the presence of coronary ischemia, LVEF at rest and with stress, end diastolic volume index (EDVI) at rest and stress and % left ventricular (LV) enlargement. Subsequent 1-year survival and development of new cardiac allograft vasculopathy (CAV) were also recorded. Those patients with abnormal CFR (<2.0) compared to those with normal CFR (≥2.0) had lower LVEF at rest and with stress, higher average end diastolic volume index (EDVI) at rest and stress and increased % left ventricular (LV) enlargement (see table). There was no difference in 1-year subsequent survival and development of new CAV. (See table) Patients with abnormal CFR (<2.0) have abnormal cardiac function and hemodynamics and may be at risk for poor outcome. Longer follow-up is required to assess for prognostic significance of an abnormal CFR.Tabled 1EndpointsCFRCFR > 2.0 (n=66)P-Value1-Year Subsequent Actual Survival96.2%97.6%0.5321-Year Subsequent Actual Freedom from CAV100.0%96.8%0.517Average LVEF Rest, Mean ± SD56.4 ± 15.8862.9 ± 11.180.028Average LVEF Post Stress, Mean ± SD60.5 ± 17.1067.4 ± 11.830.029Average EDVI Rest, Mean ± SD50.8 ± 30.3741.4 ± 14.060.044Average EDVI Post Stress, Mean ± SD55.3 ± 34.5145.2 ± 13.760.045% LV Enlargement (%)14.8% (4/27)1.5% (1/66)0.024 Open table in a new tab

Abstract 15907: Does Fractional Flow Reserve Truly Identify Coronary Stenoses Causing Myocardial Ischemia?

Background: Despite the clinical importance of coronary physiological assessment, the relationship between coronary flow reserve (CFR) and fractional flow reserve (FFR) remains poorly defined. Hypothesis: We aimed at studying the relationship between absolute CFR and FFR in patients with stable coronary artery disease (CAD). Methods: Twenty-six patients with moderate (30%-70%) pretest likelihood of CAD underwent 82Rb PET/CT cardiac imaging at rest and after pharmacological stress (dipyridamole 0.142 mg/kg/min for 4 min). CFR was considered abnormal if ≤1.74. Patients then underwent coronary angiography and FFR was measured during intracoronary administration of adenosine (200 μg). FFR was considered abnormal if ≤0.8. A total of 30 stenoses were studied. Results: A significant, albeit modest, correlation exists between CFR and FFR (r=0.44, p=0.02). In particular, of the 16 stenoses with a pathological FFR value ≤0.8, only 6 showed a reduced CFR (black dots), while the other 10 had a normal CFR (red dots); in contrast, of the 14 lesions with an FFR value above 0.8, only one showed a reduced CFR (red dot), while the other 13 had a normal CFR (black dots). Conclusions: In this preliminary series, FFR values &gt;0.8, indicating a non-significant stenosis, show an excellent correlation with absolute CFR, while pathological FFR values (&lt;0.8) poorly correlate with a reduced CFR. This discordance should be probably taken into account when facing the choice of recommending revascularization solely on the basis of FFR values.

Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity.

Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical (82)Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function.

Quantification of myocardial blood flow using dynamic 320-row multi-detector CT as compared with 15O-H2O PET

This study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against (15)O-H₂O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients. Thirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n = 7). Correlation between MBF of MDCT and PET was strong (r = 0.95, P < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P = 0.0126). CFRCT in the CAD group (2.3 ± 0.8) was significantly lower than that in the validation group (5.2 ± 1.8) (P = 0.0011). We established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP. • MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. • MBF and CFR showed good correlation between dynamic CTP and PET. • Lower CFR was well demonstrated in CAD patients by dynamic CTP.

Interrelation of RDW and coronary flow reserve in patient with idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) impairs and reduces coronary flow reserve (CFR). High level of red cell distribution width (RDW) is an independent risk factor for cardiovascular diseases. Therefore, in this observational case-control study we have aimed to determine whether RDW level is associated with CFR impairment in patients with IDC. We examined 36 patients with IDC and 35 healthy subjects formed as a control group. In addition to this, patients with IDC were divided into two subgroups according to their CFR levels [normal CFR group (CFR value ≥2) and lower CFR group (CFR value<2)]. Control and patients groups were compared using the student t-test for multiple comparisons. The subgroups were compared using the Mann-Whitney U test for continuous variables and chi-square for categorical variables. The Pearson's and Spearman correlation analysis was used to test the possible associations between CFR and the study variables as appropriate. The receiver-operating characteristic (ROC) curve was determined to evaluate the predictive performance of RDW to detect low CFR. There were no significantly differences between the lower and higher CFR groups' clinical data, baseline hemodynamic, medication and biochemical data except RDW and high-sensitivity C-reactive protein levels. We found that RDW level was a good predictor of low CFR at the receiver-operating characteristic curve. The area under the curve (AUC) was 73% (95% confidence interval between 0.56-0.90 is 95%, p: 0.018) After adjusting potential confounders include age, body-mass index, blood pressure, lipid and glucose, RDW independently associated with CFR level (Beta:-0.374; p=0.015) and hsCRP value (Beta:-0.520; p=0.001) were the independent predictors of lower CFR. Results showed that there was an independent correlation between RDW level and CFR level in patients with IDC.

Preserved Coronary Flow Reserve Effectively Excludes High-Risk Coronary Artery Disease on Angiography

Myocardial perfusion imaging has limited sensitivity for the detection of high-risk coronary artery disease (CAD). We tested the hypothesis that a normal coronary flow reserve (CFR) would be helpful for excluding the presence of high-risk CAD on angiography. We studied 290 consecutive patients undergoing (82)Rb PET within 180 d of invasive coronary angiography. High-risk CAD on angiography was defined as 2-vessel disease (≥ 70% stenosis), including the proximal left anterior descending artery; 3-vessel disease; or left main CAD (≥ 50% stenosis). Patients with prior Q wave myocardial infarction, elevated troponin levels between studies, prior coronary artery bypass grafting, a left ventricular ejection fraction of less than 40%, or severe valvular heart disease were excluded. Fifty-five patients (19%) had high-risk CAD on angiography. As expected, the trade-off between the sensitivity and the specificity of the CFR for identifying high-risk CAD varied substantially depending on the cutoff selected. In multivariable analysis, a binary CFR of less than or equal to 1.93 provided incremental diagnostic information for the identification of high-risk CAD beyond the model with the Duke clinical risk score (>25%), percentage of left ventricular ischemia (>10%), transient ischemic dilation index (>1.07), and change in the left ventricular ejection fraction during stress (<2) (P = 0.0009). In patients with normal or slightly to moderately abnormal results on perfusion scans (<10% of left ventricular mass) during stress (n = 136), a preserved CFR (>1.93) excluded high-risk CAD with a high sensitivity (86%) and a high negative predictive value (97%). A normal CFR has a high negative predictive value for excluding high-risk CAD on angiography. Although an abnormal CFR increases the probability of significant obstructive CAD, it cannot reliably distinguish significant epicardial stenosis from nonobstructive, diffuse atherosclerosis or microvascular dysfunction.

Disturbed Coronary Hemodynamics in Vessels With Intermediate Stenoses Evaluated With Fractional Flow Reserve

Background— In chronic ischemic heart disease, focal stenosis, diffuse atherosclerotic narrowings, and microcirculatory dysfunction (MCD) contribute to limit myocardial flow. The prevalence of these ischemic heart disease levels in fractional flow reserve (FFR) interrogated vessels remains largely unknown. Methods and Results— Using intracoronary measurements, 91 coronaries (78 patients) with intermediate stenoses were classified in 4 FFR and coronary flow reserve (CFR) agreement groups, using FFR&gt;0.80 and CFR&lt;2 as cutoffs. Index of microcirculatory resistance (IMR) and atherosclerotic burden (Gensini score) were also assessed. MCD was assumed when IMR≥29.1 (75 th percentile). Fifty-four (59.3%) vessels had normal FFR, from which only 20 (37%) presented both normal CFR and IMR. Among vessels with FFR&gt;0.80, most (63%) presented disturbed hemodynamics: abnormal CFR in 28 (52%) and MCD in 18 (33%). Vessels with FFR&gt;0.80 presented higher IMR [adjusted mean 27.6 (95% confidence interval, 23.4–31.8)] than those with FFR≤0.80 [17.3 (95% confidence interval, 13.0–21.7), p=0.001]. Atherosclerotic burden was inversely correlated with CFR ( r =−0.207, P =0.055), and in vessels with FFR&gt;0.80 and CFR&lt;2 (n=28, 39%), IMR had a wide dispersion (7–72.7 U), suggesting a combination of diffuse atherosclerotic narrowings and MCD. Vessels with FFR≤0.80 and normal CFR presented the lowest IMR, suggesting a preserved microcirculation. Conclusions— A substantial number of coronary arteries with stenoses showing an FFR&gt;0.80 present disturbed hemodynamics. Integration of FFR, CFR, and IMR supports the existence of differentiated patterns of ischemic heart disease that combine focal and diffuse coronary narrowings with variable degrees of MCD.

Associations of fractional pulse pressure to aortic stiffness and their impact on diastolic function and coronary flow reserve in asymptomatic diabetic patients with normal coronary angiography

We aimed to assess the relation of fractional pulse pressure (PPf) to aortic stiffness index and their impact on coronary flow reserve (CFR) and left ventricular diastolic function in asymptomatic diabetic patients. One hundred and thirty five consecutive asymptomatic diabetic patients (aged 48.8 ± 7.84 years), were included. CFR was calculated noninvasively using transthoracic echo-Doppler assessment with hyperemia induced by infusion of dipyridamole at a rate of 0.56 mg/kg over 4 min. PPf was calculated as pulse pressure divided by mean arterial pressure (SBP - DBP/MAP), while diastolic function was evaluated by means of transmitral flow and tissue Doppler imaging. Aortic stiffness indices (ASI) were measured as previously described. Diabetic patients with low CFR (n = 52) compared with those with normal CFR (n = 83) exhibited significantly increased PPf (75.2 ± 11.4 vs. 64.5 ± 6.7, p < 0.001). PPf was significantly correlated with ASI (r = 0.520, p < 0.001), E/Em ratio (r = 0.425,p < 0.001) and left atrial volume index (r = 0.462, p < 0.001). CFR was negatively correlated with both PPf (r = -0.68, p < 0.0001). After applying multivariate linear regression analysis,after correction for cardiovascular risk factors, importantly, PPf and ASI remained significant predictors of CFR (p < 0.0001 and p < 0.001, respectively). PPf was significantly correlated to ASI in asymptomatic diabetic patients. Likewise, increased PPf was associated with impaired CFR and subclinical diastolic dysfunction in diabetic patients. PPf could be utilized as a simple non-invasive predictor of occult atherosclerosis and diastolic dysfunction in diabetic patients.

GW24-e3709 Relation between adipokines and coronary flow reserve in patients with chest pain and angiographically normal arteries

ObjectivesAdipokines have been shown to play an important role in coronary heart disease (CAD). Anti-inflammatory adipokines like adiponectin and omentin protect the vessels from plaque formation. On the other hand,...

THU0320 New Parameters for Identifying Subclinical Atherosclerosis in Patients with Primary SjöGren’s Syndrome: A Pilot Study

BackgroundClinical and biochemical data suggest that autoimmune diseases are associated with endothelial dysfunction and increased atherosclerosis. We have previously shown that asymmetric dimethylarginine (ADMA) levels and coronary flow reserve (CFR)...

Relation of Coronary Flow Reserve and Diastolic Function to Fractional Pulse Pressure in Hypertensive Patients

Fractional pulse pressure (PPf), is thought to more directly reflect arterial stiffness than pulse pressure. Our aim was to evaluate the relationship between coronary flow reserve (CFR), left ventricular diastolic function (LVDf) and PPf in hypertensive patients with normal coronary arteries. Out of 109 hypertensive patients (aged 52.8 ± 9.4 years), with normal coronary angiography, CFR was calculated successfully in 106 patients. CFR was calculated using transthoracic echo Doppler assessment with hyperemia induced by infusion of dipyridamole at a rate of 0.56 mg/kg over 4 minutes, while diastolic function was evaluated by means of transmitral flow and tissue Doppler imaging. PPf was calculated as pulse pressure divided by mean arterial pressure [Systolic blood pressure - Diastolic blood pressure/Mean arterial pressure (SBP - DBP/MAP)], Hypertensive patients with low CFR (n = 54) compared with those with normal CFR (n = 52) exhibited significantly increased PPf (75.2 ± 11.4 vs. 61.5 ± 6.7 P < 0.001). Moreover, patients with higher PPf had significantly decreased transmitral E/A ratio (P < 0.01), as well as increased E/Em ratio (P < 0.01). In hypertensives with low CFR, PPf was negatively correlated with CFR (r = -0.815, P < 0.0001). After applying multivariate linear regression analysis, PPf turned out to be a powerful independent predictor of CFR. Receiver operating characteristic (ROC) analysis revealed that a PPf of ≥0.63 was the best cutoff value for prediction of CFR <2.0 and E/Em ≥ 8 (AUC = 0.916 and 0.929 respectively; P < 0.001). Increased PPf was associated with impaired CFR and diastolic dysfunction in hypertensive patients with normal coronary arteries. PPf could be used as a simple non-invasive index for assessment of coronary microcirculation in hypertensives with normal coronary arteries.

Fractional pulse pressure as a simple index of impaired coronary flow reserve in hypertensive patients

Fractional pulse pressure (PPf), is thought to be more directly reflect arterial stiffness than pulse pressure. Our aim was to evaluate the relationship between coronary flow reserve (CFR) and PPf in hypertensive patients with normal coronary arteries One-hundred and six consecutive hypertensive patients (aged 52.8 + 9.4 years), with indications of myocardial ischaemia with exercise electrocardiogram (EECG) and normal coronary arteries in coronary angiography. CFR was calculated noninvasively using transthoracic echo-Doppler assessment with hyperemia induced by infusion of dipyridamole at a rate of 0.56 mg/kg over 4 min. PPf was calculated as pulse pressure divided by mean arterial pressure (SBP-DBP/MAP), while diastolic function was evaluated by means of transmitral flow and tissue Doppler imaging. Hypertensive patients with low CFR ( n = 54) compared with those with normal CFR ( n = 52) exhibited significantly incresed PPf (75.2 ± 11.4 vs 64.5 ± 6.7 P < 0.001). In hypertensives with low CFR, CFR was negatively correlated with PPf ( r = −0.651, P < 0.0001). After applying multivariate linear regression analysis, age, left ventricular mass index, Em/Am, and PPf turned out to be independent predictors of CFR. Estimation of PPf by using simple sphygmomanometer blood pressure measurement is simple non-invasive index for assessment of coronary microcirculation in essential hypertensive patients with indications of myocardial ischaemia and normal coronary arteries.

Transthoracic measurement of left coronary artery flow reserve improves the diagnostic value of routine dipyridamole-atropine stress echocardiogram

IntroductionWe hypothesized that coronary flow reserve (CFR) in the left anterior descending artery (LAD) can be effectively measured during an accelerated dipyridamole-atropine stress echocardiography (DASE) protocol to improve the diagnostic performance of the test.Material and methodsIn 64 patients with suspected or known coronary artery disease scheduled for coronary angiography DASE with concomitant CFR measurement in LAD was performed.ResultsCoronary flow reserve measurement and calculation were feasible in 83% of patients. The positive predictive value of undetectable LAD flow was 81% for severe LAD disease. Measured values of CFR were in the range 1.3–4.1 (mean: 2.2 ±0.7). Significantly lower CFR was found in patients with LAD disease (1.97 ±0.62 vs. 2.55 ±0.57, p = 0.0015). The optimal cutoff for detecting ≥ 50% stenosis was CFR ≤ 2.1 (ROC AUC 0.776), corresponding with 68% sensitivity and 84% specificity. In patients with negative DASE results 67% of patients with LAD disease had abnormal CFR, whereas in patients with a positive DASE result 92% of patients with normal LAD had normal CFR. The DASE diagnostic accuracy for the detection of coronary artery disease (CAD) increased from 75% to 85% when CFR measurement was added to wall motion abnormality (WMA) analysis. No test with both abnormalities was false positive for the detection of coronary disease.ConclusionsIncorporation of CFR measurement into WMA-based stress echocardiography is feasible even in an accelerated DASE protocol and can be translated into an approximate gain of 10% in overall test accuracy.

Transthoracic Doppler Echocardiography for Detection of Stenoses in the Left Coronary Artery by Use of Poststenotic Coronary Flow Profiles: A Comparison with Quantitative Coronary Angiography and Coronary Flow Reserve

The aim of this study was to determine whether poststenotic diastolic-to-systolic velocity ratio (DSVR) assessed by transthoracic Doppler echocardiography could accurately identify significant stenoses in the left coronary artery. A total of 108 patients scheduled for coronary angiography because of chest pain or acute coronary syndromes were studied. The success rates of peak DSVR (pDSVR) measurements in the distal to mid left anterior descending coronary artery and marginal branches of the left circumflex coronary artery were 85% and 32%, respectively. With peak coronary flow velocity reserve as a reference, pDSVR was significantly higher in arteries with normal coronary flow reserve (peak coronary flow velocity reserve ≥ 2.0) compared with arteries with reduced coronary flow reserve (peak coronary flow velocity reserve < 2.0) (1.86 ± 0.32 vs 1.53 ± 0.31, P < .0001). In comparison with quantitative coronary angiography, pDSVR was significantly higher in lesions with diameter stenosis < 50% compared with those with diameter stenosis of 50% to 75% (1.92 ± 0.32 vs 1.53 ± 0.18, P < .0001) or diameter stenosis of 76% to 100% (1.43 ± 0.13, P < .0001). Receiver operating characteristic curves showed pDSVR < 1.68 to be the optimal cutoff value for identifying both functionally significant stenoses and diameter stenoses ≥ 50%, with sensitivity of 86% and 90%, specificity of 74% and 84%, positive predictive value of 51% and 71%, and negative predictive value of 94% and 95%, respectively. Transthoracic pDSVR measurements in the distal to mid left anterior descending coronary artery and marginal branches of the left circumflex coronary artery had high accuracy for excluding functionally significant stenoses in the left coronary artery, as well as for identifying angiographic significant stenoses.