Intermediate Coronary Artery Stenosis Research Articles

TCT-325 Influence of the amount of myocardium subtended by an intermediate coronary artery stenosis on FFR and iFR

TCT-325 Influence of the amount of myocardium subtended by an intermediate coronary artery stenosis on FFR and iFR

Diagnostic value of coronary CT angiography in comparison with invasive coronary angiography and intravascular ultrasound in patients with intermediate coronary artery stenosis: results from the prospective multicentre FIGURE-OUT (Functional Imaging criteria for GUiding REview of invasive coronary angiOgraphy, intravascular Ultrasound, and coronary computed Tomographic angiography) study

The anatomical criteria for the diagnosis of ischaemia referenced by fractional flow reserve (FFR) from non-invasive coronary computed tomographic angiography (CCTA), invasive coronary angiography (ICA), and intravascular ultrasound (IVUS) have not been evaluated contemporarily in a large-scale study. The aim of this study was to assess the diagnostic value of CCTA compared with ICA and IVUS in patients with intermediate coronary stenosis. CCTA, ICA, IVUS, and FFR were performed in 181 coronary lesions with intermediate severity. Minimal lumen diameter (MLD) and per cent diameter stenosis (%DS) were determined by CCTA and ICA, whereas minimal lumen area (MLA) was determined by CCTA and IVUS. Inducible ischaemia was defined by FFR ≤ 0.80. Diagnostic performances from non-invasive and invasive methods were compared. FFR ≤ 0.80 was observed in 49 (27.1%) lesions. CCTA MLD was smaller than ICA MLD (1.3 ± 0.5 vs. 1.5 ± 0.4 mm, P < 0.001), CCTA %DS was higher than ICA %DS (54.0 ± 14.0 vs. 50.3 ± 12.8%, P < 0.001), and CCTA MLA was smaller than IVUS MLA (2.2 ± 1.2 vs. 3.2 ± 1.2 mm(2), P < 0.001). This trend was consistent irrespective of lesion location, lesion severity, and plaque characteristics. For the determination of ischaemia, diagnostic performance of CCTA %DS was lower than ICA %DS [area under the curve (AUC) 0.657 vs. 0.765, P = 0.04], and that of CCTA MLA was lower than IVUS MLA (AUC 0.712 vs. 0.801, P = 0.03). Anatomical criteria for the diagnosis of ischaemia-producing coronary stenosis differ by non-invasive and invasive methods. Compared with invasive methods, CCTA presents overestimation in assessing lesion severity and lower diagnostic performance in assessing ischaemia.

Utility of nicorandil for the measurement of coronary fractional flow reserve

Nicorandil, an adenosine triphosphate (ATP)-sensitive potassium channel opener, has been used as an anti-angina drug that causes coronary vasodilation of both epicardial and resistance vessels. We assessed the hyperaemic efficacy of nicorandil for the measurement of coronary fractional flow reserve (FFR). In this prospective, single-centre study, we enrolled 20 consecutive patients (20 lesions) with intermediate coronary artery stenosis. Hyperaemic efficacy of intracoronary bolus injection of nicorandil (2mg) was compared with that of continuous intravenous infusion of adenosine triphosphate (ATP, 150μg/kg/min). The intra-patient difference of FFR value between the two hyperaemic stimuli was evaluated using a non-inferiority design with the margin of 0.03. Among study patients, no serious event occurred with administration of either stimulus. A strong and linear correlation of FFR with ATP and nicorandil was observed (r (2)=0.98, P<0.0001). The intra-patient difference of the FFR between nicorandil and ATP was 0.003 (95% confidence interval -0.004 to 0.011), and the probability for the non-inferiority margin of 0.03 was <0.0001. In conclusion, bolus intracoronary injection of nicorandil was non-inferior to continuous intravenous injection of ATP in achieving maximal hyperaemia. Nicorandil could be considered as an alternative option for achieving maximal coronary and myocardial hyperaemia for the assessment of FFR.

Non-invasively assessed coronary flow reserve stratifies outcomes in patients with intermediate left main coronary artery stenosis

Background: Correct assessment of the significance of left main coronary artery (LMCA) stenosis on the basis of clinical and angiographic information alone often cannot be done reliably and requires assessment of functional significance of lesions observed on coronary angiography. Aim: The aim of this study was to determine the prognostic value of noninvasively measured coronary flow reserve (CFR) in patients with angiographically assessed intermediate or equivocal LMCA stenosis during long-term follow up. Methods: Hundred patients (59±9 years, 80 male) in whom LMCA was assessed by coronary angiography to be ≤50% diameter stenosis; without significant left anterior descending artery stenosis (LAD), were included in this prospective follow-up study. All patients underwent transthoracic Doppler echocardiography measurements of CFR in medial part of LAD after intravenous adenosine administration to assess functional significance of LMCA stenosis. CFR values were calculated as the ratio between hyperemic maximal flow velocity and resting flow velocity. Patients were followed for the mean period of 27±10 months for the occurrence of composite end point including cardiovascular death, myocardial infarction, hospitalization due to unstable angina and clinically guided revascularization. Results: 91 patient completed follow-up. Events occurred in 16. Mean CFR value of 1.80±0.44 for patients having events was significantly lower, compared to those who were free of events where mean CFR value was 2.4±0.44 (p<0.001). During the follow up period (range 1-50 months), 69 patients (95, 8%) with CFR ≥2 remained free of death and major adverse events vs. 6 patients (31,6%) with CFR <2, p<0.001. By Kaplan-Meier method, at 24 months the percent estimated survival free from cardiac related events was 95±3% in patients with CFR ≥2 and 45±11% in patients with CFR <2, p<0.001. Picture Conclusion: In patients with intermediate or equivocal left main coronary artery disease, CFR ≥2 is associated with low event rate and excellent survival. According to our results CFR measured by transthoracic Doppler echocardiography provides reliable and precise, yet non-invasive tool for the assessment of functional severity of LMCA disease that carries significant prognostic information in long-term follow-up.

Myocardial CT perfusion imaging improves diagnostic accuracy of coronary CT angiography especially in patients with intermediate severity coronary artery stenoses

Purpose: The purpose of this study was to evaluate whether adenosine-stress myocardial CT perfusion (CTP) in addition to CT angiography (CTA) improves the positive predictive value (PPV) of CT for diagnosing significant coronary artery stenoses in patients with recent acute-onset chest pain. Methods: Consecutive patients hospitalised with acute chest pain, but normal electrocardiogram and cardiac biomarkers were scheduled for CTP on top of CTA. Among patients referred for invasive coronary angiography (ICA), a per patient and per vessel analysis for the detection of coronary stenoses by CTA and reversible perfusion defects by CTP was performed. ICA including fractional flow reserve (FFR) for intermediate stenosis was used as a reference method. For the per vessel analysis, PPV was evaluated for intermediate (50-70%) and severe (>70%) coronary lesions as defined by CTA, and negative predictive value (NPV) for mild (0-49%) coronary lesions. Results: Both CTA and CTP were performed in 34 patients scheduled for ICA. ICA found significant coronary stenoses in 21 patients (62%) and per patient PPV was 76% for CTA increasing to 90% for combined CTA+CTP. Area under the curve (AUC) was 0.72 for CTA and 0.88 for CTA+CTP (p=0.02). In the per vessel analysis significant coronary stenoses were found on ICA in 32 vessels (31%), and PPV for CTA was 69% increasing to 97% for CTA+CTP. AUC was 0.88 for CTA and 0.96 for CTA+CTP (p=0.006). Of 102 vessels, CTA found mild coronary lesions in 56 vessels (55%), intermediate lesions in 15 vessels (15%) and severe lesions in 31 vessels (30%). In intermediate lesions by CTA, ICA/FFR confirmed a significant stenosis in 2/15 vessels (PPV= 13%), and for CTA+CTP PPV increased to 75%. In severe lesions by CTA, ICA confirmed a significant stenosis in 30/31 vessels (PPV=97%) and for CTA+CTP PPV was 100%. NPV was 98% for mild CTA lesions, without any additional contribution of CTP. Conclusion: In patients with recent acute-onset chest pain myocardial CT perfusion has incremental diagnostic value in addition to CT-angiography for diagnosing significant coronary stenoses. CT perfusion appears to be most beneficial in the assessment of intermediate coronary stenoses.

Use of regadenoson for measurement of fractional flow reserve

To compare the use of regadenoson to adenosine for measurement of fractional flow reserve (FFR). FFR is an accepted method to assess the functional significance of intermediate coronary artery stenoses and uses adenosine to induce maximal hyperemia. The use of the selective A2a receptor agonist regadenoson for FFR is not established. Fifty-seven patients undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was achieved by a standard intravenous adenosine infusion (140 mcg/kg/min). After a washout period of 10 min, FFR was reassessed using regadenoson as a single 0.4 mg intravenous bolus. FFR measurements were recorded at baseline and following maximal hyperemia with both agents. Mean age was 57 ± 8 years and 47 were male. Sixty coronary lesions were evaluated and were located in the left anterior descending in 34, the left circumflex in 9, right coronary in 15, and left main coronary artery in 2. Mean ( ± SD) FFR following adenosine and regadenoson was 0.79 ( ± 0.09) and 0.79 (±0.09), respectively, P = NS. Time to FFR nadir was shorter with regadenoson compared to adenosine, 36.6 ± 24 versus 66 ± 0.19 sec, P < 0.0001, respectively. No patients experienced any significant side effects related to regadenoson. Regadenoson is a viable alternative to intravenous adenosine for achieving maximal hyperemia during FFR assessment. Compared to adenosine, regadenoson has a similar hemodynamic response, achieves more rapid hyperemia, is easier to use, and has an excellent side-effect profile.

Usefulness of lumen area parameters determined by intravascular ultrasound to predict functional significance of intermediate coronary artery stenosis

Background Coronary artery disease is the leading cause of death in China. Percutaneous coronary intervention is a recent milestone technology for treatment coronary artery disease. However, clinical decision making for patients with intermediate coronary stenosis is still controversial. We designed this study to assess the optimal intravascular ultrasound (IVUS) criteria for predicting functional significance of intermediate coronary lesions. Methods We enrolled 141 patients with 165 intermediate coronary lesions located in vessels with a diameter ≥ 2.50 mm. IVUS of intermediate coronary lesions were performed before intervention. Pressure-derived fractional flow reserve (FFR) was measured at maximal hyperemia induced by adenosine infusion. An FFR &lt;0.80 was considered as abnormal functional significance. Results For the overall 165 lesions, the mean FFR value was 0.84±0.09. The diameter of the stenosis by visual estimation on angiogram was (59.63±11.29)%. Minimum lumen diameter (MLD), minimum lumen area (MLA) and plaque burden (PB) were (2.00±0.36) mm, (3.88±1.34) mm2, (67.28±9.89)% respectively by IVUS measurements. An FFR &lt;0.80 was seen in 43 lesions (30.5%). There was a moderate correlation between IVUS parameters and FFR, including MLD (r=0.372, P &lt;0.001), MLA (r=0.442, P &lt;0.001) and PB (r=-0.172, P &lt;0.05). MLA was a predictor for FFR as a continuous variable independent of possible confounding variables (P &lt;0.05), and MLA and PB, were predictors for FFR &lt;0.80 as binary variables (P &lt;0.05). The best cutoff value of MLA to predict FFR &lt;0.80 was &lt;3.15 mm2, with a 73.6% diagnostic accuracy; sensitivity 71.4%, specificity 67.0%, AUC=0.709, and P &lt;0.001. The cutoff value of the PB to predict FFR &lt;0.80 was 65.45%; sensitivity 82.6%, specificity 41.2%, AUC=0.644, and P &lt;0.01. If both MLA and PB were taken into account, the negative predictive value and the positive predictive value were 88.7% and 64.8% respectively. Conclusions Anatomic measurements of intermediate coronary lesions obtained by IVUS showed a moderate correlation to FFR values. IVUS-derived MLA ≥3.15 mm2 may be useful to exclude FFR &lt;0.80, but poor specificity limits its applicability for physiological assessment of lesions &lt;3.15 mm2. MLA was one of many factors affecting coronary flow hemodynamics. Both MLA and PB should be taken into account when determining functional ischemia.

Validation of Fractional Flow Reserve in Intermediate Left Main Coronary Artery Stenosis

Validation of Fractional Flow Reserve in Intermediate Left Main Coronary Artery Stenosis

Comparison of intravenous adenosine and intravenous regadenoson for the measurement of pressure-derived coronary fractional flow reserve

Defining the clinical and physiologic significance of an intermediate coronary artery stenosis is aided by measurement of fractional flow reserve (FFR). Adenosine is the most common agent used in the cardiac catheterisation laboratory for the measurement of FFR. Regadenoson, a selective adenosine receptor agonist, with fewer side effects than adenosine has been used extensively in stress testing to induce hyperaemia. We postulated that FFR measurements would be equivalent following administration of regadenoson and adenosine. Twenty patients with an angiographic intermediate coronary artery stenosis (50% to 80%) were included in the study. FFR was measured during three minutes of intravenous (IV) adenosine infusion and for five minutes after an injection of regadenoson. The mean difference between the FFR measured by IV adenosine and IV regadenoson was 0.0040 (min -0.04, max +0.04, standard deviation [SD] 0.025). There was a strong linear correlation between the FFR measured by IV adenosine and IV regadenoson (R2 linear=0.933). The FFR at maximum hyperaemia was achieved earlier using regadenoson than adenosine (59±24.5 sec vs. 93±44.5 sec, p=0.01). Regadenoson produces similar pressure-derived FFR compared to IV adenosine infusion.

Quantitative evaluation improves specificity of myocardial perfusion SPECT in the assessment of functionally significant intermediate coronary artery stenoses: a comparative study with fractional flow reserve measurements

Myocardial perfusion SPECT (MPS) is a noninvasive method commonly used for assessment of the hemodynamic significance of intermediate coronary stenoses. Fractional flow reserve (FFR) measurement is a well-validated invasive method used for the evaluation of intermediate stenoses. We aimed to determine the association between MPS and FFR findings in intermediate degree stenoses and evaluate the added value of quantification in MPS. Fifty-eight patients who underwent intracoronary pressure measurement in the catheterization laboratory to assess the physiological significance of intermediate (40-70%) left anterior descending (LAD) artery lesions, and who also underwent stress myocardial perfusion SPECT either for the assessment of an intermediate stenosis or for suspected coronary artery disease were analyzed retrospectively in the study. Quantitative analysis was performed using the 4DMSPECT program, with visual assessment performed by two experienced nuclear medicine physicians blinded to the angiographic findings. Summed stress scores (SSS) and summed difference scores (SDS) in the LAD artery territory according to the 20 segment model were calculated. A summed stress score of ≥ 3 and an SDS of ≥ 2 were assumed as pathologic, indicating significance of the lesion; a cutoff value of 0.75 was used to define abnormal FFR. Both visual and quantitative assessment results were compared with FFR using Chi-square (χ²) test. The mean time interval between two studies was 13 ± 11 days. FFR was normal in 45 and abnormal in 13 patients. Considering the FFR results as the gold standard method for assessing the significance of the lesion, the sensitivity and specificity of quantitative analysis determining the abnormal flow reserve were 85 and 84%, respectively, while visual analysis had a sensitivity of 77% and a specificity of 51%. There was a good agreement between the observers (κ = 0.856). Summed stress and difference scores demonstrated moderate inverse correlations with FFR values (r = -0.542, p < 0.001 and r = -0.506, p < 0.001, respectively). Quantitative analysis of the myocardial perfusion SPECT increases the specificity in evaluating the significance of intermediate degree coronary lesions.

Abstract 18406: Gender Influence on the Functional Significance of Intermediate Coronary Artery Stenosis

Background Previous studies suggest that there are clinically relevant differences between women and men in patients with ischemic heart disease. However, little is known about the gender influence on the functional significance of coronary artery stenosis. Method A total of 1,032 lesions with available intravascular ultrasound (IVUS) and fractional flow reserve (FFR) were recruited from 11 international centers and 881 de novo lesions with intermediate stenosis located at the non-left main major epicardial coronary arteries (822 patients, male 70.6%) were included in this analysis. All data were analyzed at Seoul National University Data Management Core Laboratory. FFR ≤0.8 was considered functionally significant. Results Angiographic % diameter stenosis and reference diameter were 49.6±12.7 and 3.0±0.5 mm, respectively. Minimum luminal area (MLA) by IVUS was 3.12±1.34mm 2 . Mean FFR was 0.81±0.11 and 353 lesions (40.1%) were functionally significant. There were no differences in angiographic lesion severity and IVUS MLA between male and female patients (Table). However, compared to female patients, FFR was significantly lower in male (male: 0.81±0.11 vs. female: 0.83±0.10, P =0.010) and functionally significant stenosis was more frequent in male patients (FFR ≤0.8; male: 42.8% vs. female: 32.9%, P =0.007). The best cutoff value of angiographic % diameter stenosis to determine the functional significance was 49.4% in male and 53.0% in female patients. The best cutoff value of IVUS MLA was 3.25 mm 2 in male and 3.05 mm 2 in female patients. Conclusion Compared to male patients, female patients may have higher anatomical threshold for the functional significance of coronary artery stenosis.

Should we be using fractional flow reserve more routinely to select stable coronary patients for percutaneous coronary intervention?

To address the clinical benefit of fractional flow reserve (FFR) measurement in stable coronary artery disease (CAD) patients. The efficacy of revascularization in patients with stable CAD has been debatable. However, there has been consensus that revascularization for ischemic-producing lesions may improve clinical outcomes. FFR is considered nowadays as the gold standard for the invasive assessment of ischemic potential of intermediate coronary artery stenosis. Intermediate stenosis with FFR of greater than 0.80 has been demonstrated to be safely deferred with annual event rate less than 1%. Recently, preliminary data of FAME II trial presented that revascularization for stenosis with FFR of 0.80 or less has clinical benefits over optimal medical treatment with respect to the reduction of unplanned hospitalization and urgent revascularization in stable CAD patients. A large randomized controlled trial demonstrated that FFR-guided percutaneous coronary intervention (PCI) improved clinical outcomes while reducing the medical costs in multivessel CAD. Therefore, current guidelines recommend the consideration of FFR measurements as level of evidence 'A' when the ischemic potential for specific target lesions is questionable. Much clinical evidence indicates that use of this dedicated invasive functional method may help in selecting appropriate patients and lesions for treatment, avoiding unnecessary procedures, reducing medical costs, and improving each patient's clinical outcomes. Therefore, we should use FFR more routinely to select stable coronary patients for PCI.

Comparison of Two- and Three-Dimensional Quantitative Coronary Angiography to Intravascular Ultrasound in the Assessment of Intermediate Left Main Stenosis

Angiographic evaluation of intermediate left main coronary artery stenosis (LMS) is often limited. Three-dimensional (3D) quantitative coronary angiography has recently developed to overcome 2-dimensional (2D) quantitative coronary angiographic (QCA) limitations. In patients with angiographically intermediate LMS, we investigated whether 3D quantitative coronary angiography was superior to 2D quantitative coronary angiography in predicting the presence of a significant LMS, defined as a minimum luminal area <6 mm(2) at intravascular ultrasound (IVUS). 2D and 3D quantitative coronary angiography were compared in their measurements of minimum luminal area, percent area stenosis, minimum luminal diameter, and percent diameter stenosis and in their prediction of an IVUS minimum luminal area <6 mm(2). In total 58 target lesions were interrogated, 25 (43%) of which had an IVUS minimum luminal area <6 mm(2). Correlation between 3D-QCA minimum luminal area and IVUS minimum luminal area was stronger than the correlation between 2D-QCA minimum luminal area (or minimum luminal diameter) and IVUS minimum luminal area (R = 0.67, p = 0.0001, and R = 0.40, p = 0.001, respectively, p = 0.04 for comparison). To predict IVUS minimum luminal area <6 mm(2), the most accurate 2D-QCA measurement was minimum luminal diameter (area under curve 0.81, cutoff 2.2 mm, p = 0.0001), and the most accurate 3D-QCA measurement was minimum luminal area (area under curve 0.86, cutoff 5.6 mm(2), p = 0.0001). 2D-QCA percent diameter stenosis did not significantly predict IVUS minimum luminal area <6 mm(2) (area under curve 0.56, cutoff 38%, p = 0.45). In conclusion, the accuracy of quantitative coronary angiography in predicting LM IVUS minimum luminal area <6 mm(2) is limited. When IVUS is not available or contraindicated, 3D quantitative coronary angiography may assist in the evaluation of intermediate LMS. Among 2D-QCA parameters, minimum luminal diameter is more accurate than percent diameter stenosis in predicting significant LMS.

Intravascular ultrasound lumen area parameters for assessment of physiological ischemia by fractional flow reserve in intermediate coronary artery stenosis

A fractional flow reserve (FFR) of <0.8 is currently used to guide revascularization in lesions with intermediate coronary stenosis. Whether there is an intravascular ultrasound (IVUS) measurement or a cutoff value that can reliably determine which of these intermediate lesions requires intervention is unclear. We assessed IVUS measurement accuracy in defining functional ischemia by FFR. The analysis included 205 intermediate lesions (185 patients) located in vessel diameters >2.5 mm. Positive FFR was considered present at <0.8. IVUS measurements were correlated to the FFR findings in intermediate lesions with 40%-70% stenosis. Fifty-four (26.3%) lesions had FFR<0.8. There was moderate correlation between FFR and IVUS measurements, including minimum lumen area (MLA) (r=0.36, P<.001), minimum lumen diameter (MLD) (r=0.25, P=<.001), lesion length (r=-0.43, P<.001), and area stenosis (r=-0.33, P=.01). A receiver operating characteristic curve (ROC) identified MLA<3.09 mm(2) (sensitivity 69.2%, specificity 79.5%) as the best threshold value for FFR<0.8. The correlation between FFR and IVUS was better for large vessels compared to small vessels. ROC analysis identified the best threshold value for FFR<0.8 of MLA<2.4 mm(2) [area under curve (AUC)=0.74] in lesions with reference vessel diameters of 2.5-3 mm, MLA<2.7 mm(2) (AUC=0.77) in lesions with reference vessel diameters of 3-3.5 mm, and MLA<3.6 mm(2) (AUC=0.70) in lesions with reference vessel diameters >3.5 mm. Anatomic measurements of intermediate coronary lesions obtained by IVUS show a moderate correlation to FFR values. The correlation was better for larger-diameter vessels. Vessel size should always be taken into account when determining the MLA associated with functional ischemia.

Clinical Utility of Regadenoson for Assessing Fractional Flow Reserve

The aim of this study was to evaluate the efficacy of regadenoson, in comparison with adenosine, for assessing fractional flow reserve (FFR) of intermediate coronary artery stenoses (CAS). Fractional flow reserve is an established invasive method for assessing the physiological significance of CAS. Regadenoson, a selective A(2A) receptor agonist, is an approved hyperemic agent for pharmacological stress imaging, but its role for measuring FFR is unknown. This prospective, single-center study enrolled 25 consecutive patients with intermediate CAS discovered during elective angiography (25 lesions). In each patient, FFR of the CAS was measured first by IV adenosine (140 μg/kg/min), followed by IV regadenoson (400 μg bolus). The intrapatient FFR correlation between adenosine and regadenoson was evaluated. The mean age was 63 ± 11 years, and mean left ventricular ejection fraction was 58 ± 11%. Most patients were male (52%) and had hypertension (84%) and dyslipidemia (84%), with 24% having diabetes mellitus and 20% chronic obstructive pulmonary disease. The CAS was visually estimated during angiography (mean 58 ± 9%) and most often found in the left anterior descending coronary artery (48%). A strong, linear correlation of FFR was noted with adenosine and regadenoson (r = 0.985, p < 0.001). A hemodynamically significant lesion (FFR ≤ 0.80) was present in 52% with no reclassification of significance between adenosine and regadenoson. No serious events occurred with administration of either drug. Our results suggest that a single IV bolus of regadenoson is as effective as an intravenous infusion of adenosine for measuring FFR and, given its ease of use, should be considered for FFR measurement in the catheterization laboratory.

Buddy Wire Technique to Facilitate Fractional Flow Reserve of an Ostial Right Coronary Artery Lesion

Fractional flow reserve (FFR) is a well-established method to assess the hemodynamic and clinical significance of intermediate coronary artery stenoses. Ostial coronary lesions present a particular challenge to FFR measurements, as the guide needs to be positioned outside the artery during normalization and hyperemia measurements. Utilization of a “buddy wire” can help maintain stability of the coronary guide to facilitate FFR measurements of ostial coronary lesions.

Optimal Intravascular Ultrasound Criteria and Their Accuracy for Defining the Functional Significance of Intermediate Coronary Stenoses of Different Locations

We performed this study to determine the optimal intravascular ultrasound (IVUS) criteria and to evaluate their accuracy for defining the functional significance of intermediate coronary stenoses in different locations of the coronary tree. Presence of myocardial ischemia is the most important prognostic factor in patients with coronary artery disease and is determined by both the lesion severity and the amount of myocardium supplied. IVUS and fractional flow reserve (FFR) measurements were performed in 267 intermediate lesions located at the proximal or mid part of major epicardial coronary arteries. Optimal IVUS criteria and their diagnostic accuracy for functionally significant stenoses (FFR <0.8) were assessed. FFR was <0.8 in 88 lesions (33%). The determinants of FFR were minimum lumen area (MLA) and lesion location. The diagnostic accuracy of MLA was highly variable according to the location of lesions. The best cutoff value of MLA to define the functional significance was 3.0 mm(2) (area under the curve [AUC]: 0.81, 95% confidence interval [CI]: 0.68 to 0.91) for proximal left anterior descending artery (LAD) lesions and 2.75 mm(2) for mid-LAD lesions located before the second diagonal branch (AUC: 0.76, 95% CI: 0.66 to 0.84). However, the appropriate MLA to predict the functional significance of lesions could not be found in other segments. When IVUS parameters are used to determine the functional significance of lesions in patients with intermediate coronary artery stenoses, different criteria should be used according to lesion location. In segments or vessels with anatomic variations, IVUS cannot be used for functional assessment of a stenosis. (Comparison of Fractional Flow Reserve and Intravascular Ultrasound; NCT01133015).

Correlation between fractional flow reserve and intravascular ultrasound lumen area in intermediate coronary artery stenosis

Fractional flow reserve (FFR) of <0.8 or 0.75 is currently used to guide revascularisation in lesions with intermediate coronary stenosis. We assessed whether there is an intravascular ultrasound (IVUS) measurement that can reliably be used to predict when patients should undergo intervention. The analysis included 92 intermediate lesions (84 patients) located in vessel diameters >2.5 mm. Positive FFR was considered present at <0.8 and 0.75. IVUS minimum lumen area (MLA) was correlated to the FFR findings in intermediate lesions with 40-70% stenosis. The mean FFR value was 0.89 ± 0.08. Twenty-four patients (26.1%) had FFR <0.8; 17 (18.5%) <0.75. Positive correlations between FFR and IVUS measurements included MLA (r = 0.34, p<0.001), minimum lumen diameter (MLD) (r=0.31, p=0.004), lesion length (r=-0.5, p<0.001), and area stenosis (r=-0.31, p=0.01). There was no significant correlation between FFR and quantitative coronary angiography in MLD (r=0.19, p=0.06), diameter stenosis (r=0.08, p=0.4), or lesion length (r=-0.14, p=0.17). A receiver operating characteristic curve identified MLA <2.8 mm2 (sensitivity 79.7%, specificity 80.3%) as the best threshold value for FFR <0.75; and MLA <3.2 mm2 as best for FFR <0.8 (sensitivity 69.2%, specificity 68.3%). Anatomic measurements of intermediate coronary lesions obtained by IVUS show a moderate correlation to FFR values, although they differ according to vessel size. IVUS MLA may be used as an alternative to FFR when assessing the need for intervention in intermediate coronary lesion. Vessel size, however, should always be taken into account.

Correlation between fractional flow reserve and intravascularultrasound lumen area in intermediate coronary artery stenosis

Clinical trials testing proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have demonstrated an unanticipated but significant lipoprotein (a) (Lp(a))-lowering effect, on the order of 25% to 30%. Although the 50% to 60% reduction in low-density lipoprotein (LDL)-cholesterol (LDL-C) achieved by PCSK9i is mediated through its effect on LDL receptor (LDLR) preservation, the mechanism for Lp(a) lowering is unknown.We sought to characterize the degree of concordance between LDL-C and Lp(a) lowering because of PCSK9i in a standard of care patient cohort.Participants were selected from our Center for Preventive Cardiology, an outpatient referral center in a tertiary academic medical center. Subjects were included in this study if they had (1) at least 1 measurement of LDL-C and Lp(a) before and after initiation of the PCSK9i; (2) baseline Lp(a) > 10 mg/dL; and (3) continued adherence to PCSK9i therapy. They were excluded if (1) they were undergoing LDL apheresis; (2) pre- or post-PCSK9i LDL-C or Lp(a) laboratory values were censored; or (3) subjects discontinued other lipid-modifying therapies. In total, 103 subjects were identified as taking a PCSK9i and 26 met all inclusion and exclusion criteria. Concordant response to therapy was defined as an LDL-C reduction >35% and an Lp(a) reduction >10%.The cohort consisted of 26 subjects (15 females, 11 males, mean age 63 ± 12 years). Baseline mean LDL-C and median Lp(a) levels were 167.4 ± 72 mg/dL and 81 mg/dL (interquartile range 38–136 mg/dL), respectively. The average percent reductions in LDL-C and Lp(a) were 52.8% (47.0–58.6) and 20.2% (12.2–28.1). The correlation between %LDL and %Lp(a) reduction was moderate, with a Spearman's correlation of 0.56 (P < .01). All subjects except for 1 had a protocol-appropriate LDL-C response to therapy. However, only 16 of the 26 (62%; 95% confidence interval 41%–82%) subjects had a protocol-concordant Lp(a) response. Although some subjects demonstrated negligible Lp(a) reduction associated with PCSK9i, there were some whose Lp(a) decreased as much as 60%.In this standard-of-care setting, we demonstrate moderate correlation but large discordance (∼40%) in these 2 lipid fractions in response to PCSK9i. The results suggest that pathways beyond the LDLR are responsible for Lp(a) lowering and indicate that PCSK9i have the potential to significantly lower Lp(a) in select patients, although confirmation in larger multicenter studies is required.

Assessment of flow velocity in saphenous vein graft using the Doppler guidewire

The purpose of the study is to evaluate flow velocity characteristics in saphenous vein graft for coronary artery bypass grafting, especially in the graftnative vessel anastomotic site. The flow velocity was measured in 13 patients with saphenous vein graft (Group I) using a Doppler guidewire, and values were compared with those in patients who had severe (≧75%, Group II, n=31) or intermediate (<75%, Group III, n=27) coronary artery stenosis. In Group I, the flow velocity data were measured in the graft, in the anastomotic site, and in the native artery distal to the anastomosis, and in Groups II and III data were measured proximal to the stenosis, in the stenosis, and distal to the stenosis. In the saphenous vein graft, average peak velocity (APV) was significantly lower than that proximal to the stenosis. The APV increased significantly from the graft to the anastomotic site (13.3±7.2 → 36.2±15.8 cm/s,p<0.001). The APV in the anastomotic site was significantly lower than that in the stenotic site in Group II (Group II: 100.5±54.7 cm/s,p<0.001), but it was similar to that in Group III (Group III: 58.6±25.2 cm/s). The APV distal to the anastomosis in Group I was normal (22.4±8.0 cm/s), and it was significantly faster than the APV distal to the stenosis in Group II (Group II: 11.7±8.0 cm/s,p <0.001) or Group III (Group III: 15.9±8.2 cm/s,p< 0.05). In Group I, the diameter of saphenous vein graft was significantly larger than that of the native distal artery (4.23±0.85 vs 2.06±0.17 mm,p<0.001), and the Doppler-derived percent cross-sectional area stenosis at the anastomosis showed a significant correlation with the angiographically derived percent crosssectional area stenosis of the graft to the native distal artery (r=0.95,p<0.001). From these results it was thought that the increase of the APV from the graft to the anastomosis was due to caliber change from the graft to the native artery.