Quantification of coronary microvascular resistance using angiographic images for volumetric blood flow measurement: in vivo validation

Structural coronary microcirculation abnormalities are important prognostic determinants in clinical settings. However, an assessment of microvascular resistance (MR) requires a velocity wire. A first-pass distribution analysis technique to measure volumetric blood flow has been previously validated. The aim of this study was the in vivo validation of the MR measurement technique using first-pass distribution analysis. Twelve anesthetized swine were instrumented with a transit-time ultrasound flow probe on the proximal segment of the left anterior descending coronary artery (LAD). Microspheres were injected into the LAD to create a model of microvascular dysfunction. Adenosine (400 μg·kg(-1)·min(-1)) was used to produce maximum hyperemia. A region of interest in the LAD arterial bed was drawn to generate time-density curves using angiographic images. Volumetric blood flow measurements (Q(a)) were made using a time-density curve and the assumption that blood was momentarily replaced with contrast agent during the injection. Blood flow from the flow probe (Q(p)), coronary pressure (P(a)), and right atrium pressure (P(v)) were continuously recorded. Flow probe-based normalized MR (NMR(p)) and angiography-based normalized MR (NMR(a)) were calculated using Q(p) and Q(a), respectively. In 258 measurements, Q(a) showed a strong correlation with the gold standard Q(p) (Q(a) = 0.90 Q(p) + 6.6 ml/min, r(2) = 0.91, P < 0.0001). NMR(a) correlated linearly with NMR(p) (NMR(a) = 0.90 NMR(p) + 0.02 mmHg·ml(-1)·min(-1), r(2) = 0.91, P < 0.0001). Additionally, the Bland-Altman analysis showed a close agreement between NMR(a) and NMR(p). In conclusion, a technique based on angiographic image data for quantifying NMR was validated using a swine model. This study provides a method to measure NMR without using a velocity wire, which can potentially be used to evaluate microvascular conditions during coronary arteriography.     

Assessment of coronary microcirculation in a swine animal model

Coronary microvascular dysfunction has important prognostic implications. Several hemodynamic indexes, such as coronary flow reserve (CFR), microvascular resistance, and zero-flow pressure (P(zf)), were used to establish the most reliable index to assess coronary microcirculation. Fifteen swine were instrumented with a flow probe, and a pressure wire was advanced into the distal left anterior descending artery. Adenosine was used to produce maximum hyperemia. Microspheres were used to create microvascular dysfunction. An occluder was used to produce stenosis. Blood flow from the probe (Q(p)), aortic pressure, distal coronary pressure, and right atrium pressure were recorded. Angiographic flow (Q(a)) was calculated using a time-density curve. Flow probe-based CFR and angiographic CFR were calculated using Q(p) and Q(a), respectively. Flow probe-based (NMR(qh)) and angiographic normalized microvascular resistance (NMR(ah)) were determined using Q(p) and Q(a), respectively, during hyperemia. P(zf) was calculated using Q(p) and distal coronary pressure. Two series of receiver operating characteristic curves were generated: normal epicardial artery model (N model) and stenosis model (S model). The areas under the receiver operating characteristic curves for flow probe-based CFR, angiographic CFR, NMR(qh), NMR(ah), and P(zf) were 0.855, 0.836, 0.976, 0.956, and 0.855 in N model and 0.737, 0.700, 0.935, 0.889, and 0.698 in S model. Both NMR(qh) and NMR(ah) were significantly more reliable than CFR and P(zf) in detecting the microvascular deterioration. Compared with CFR and P(zf), NMR provided a more accurate assessment of microcirculation. This improved accuracy was more prevalent when stenosis existed. Moreover, NMR(ah) is potentially a less invasive method for assessing coronary microcirculation.     

Use and limitations of magnetic resonance phase-contrast assessment of coronary flow reserve in a model of collateral dependence

Phase-contrast magnetic resonance imaging (PC-MRI) is useful for assessing coronary artery flow reserves (CFR) in man and acute animal models with intermediate coronary lesions. The present study examines the use of PC-MRI for assessing CFR in a model with critical stenosis and collateral dependence. PC-MRI quantitative flow measurements from the proximal left anterior descending (LAD) and left circumflex (LCX) coronary arteries were compared with myocardial tissue perfusion reserve measurements (microsphere techniques) after placement of a 2.25-mm ameroid constrictor on the proximal LCX in a porcine model; measurements were obtained at implantation (n = 4) and at 3 to 4 weeks (n = 4) and 6 weeks (n = 5) postimplantation. CFR is defined as the ratio of maximal hyperemic flow to baseline flow. Hyperemia was induced using intravenous adenosine (140 mg/kg/min). Collateral dependence in the LCX distri bution was evidenced by angiographic findings of critical stenosis with minimal myocardial histological changes and normal baseline myocardial perfusion (microsphere techniques). In this setting, PC-MRI CFR was correlated with microsphere measures of perfusion reserve. Collateral dependence was confirmed by Evan's blue dye injection. This study provides angiographic, myocardial perfusion, and histological correlates associated with PC-MRI epicardial CFR changes during chronic, progressive coronary artery constriction. It also demonstrates the disparity between epicardial and myocardial measures of coronary flow reserve with collateral dependence and the caveats for PC-MRI use in models of progressive coronary constriction.     

Delineating the guide-wire flow obstruction effect in assessment of fractional flow reserve and coronary flow reserve measurements

Hemodynamic analysis was conducted to determine uncertainty in clinical measurements of coronary flow reserve (CFR) and fractional flow reserve (FFR) over pathophysiological conditions in a patient group with coronary artery disease during angioplasty. The vasodilation-distal perfusion pressure (CFR-p(rh)) curve was obtained for 0.35- and 0.46-mm guide wires. Our hypothesis is that a guide wire spanning the lesions elevates the pressure gradient and reduces the flow during hyperemic measurements. Maximal CFR-p(rh) was uniquely determined by the intersection of measured CFR and calculated p(rh) of native and residual epicardial lesions in patients without microvascular disease, during angioplasty. Extrapolation of the linear curve gave a zero-coronary flow mean pressure (p(zf)) of approximately 20 mmHg and a corresponding p(rh) of 55 mmHg in the native lesions, which coincided with the level that causes ischemia in human hearts. On this linear curve, values of CFR and FFRmyo (pathophysiological condition) and CFRg and FFRmyog (in the presence of the guide wire) were obtained in native and residual lesions. A strong linear correlation was found between CFR and CFRg [CFR = CFRg x 0.689 + 1.271 (R2= 0.99) for 0.46 mm and CFR = CFRg x 0.757 + 1.004 (R2= 0.99) for 0.35 mm] and between FFRmyo and FFRmyog [FFRmyo = FFRmyog x 0.737 + 0.263 (R2= 0.99) for 0.46 mm and FFRmyo = FFRmyog x 0.790 + 0.210 (R2= 0.99) for 0.35 mm]. This study establishes a strong correlation between CFR and CFRg and between FFRmyo and FFRmyog, which could be used to obtain the true state of occlusion in the coronary artery during angioplasty.     

Increased basal coronary blood flow as a cause of reduced coronary flow reserve in diabetic patients

A reduced coronary flow reserve (CFR) has been demonstrated in diabetes, but the underlying mechanisms are unknown. We assessed thermodilution-derived CFR after 5-min intravenous adenosine infusion through a pressure-temperature sensor-tipped wire in 30 coronary arteries without significant lumen reduction in 30 patients: 13 with and 17 without a history of diabetes. We determined CFR as the ratio of basal and hyperemic mean transit times (T(mn)); fractional flow reserve (FFR) as the ratio of distal and proximal pressures at maximal hyperemia to exclude local macrovascular disease; and an index of microvascular resistance (IMR) as the distal coronary pressure at maximal hyperemia divided by the inverse of the hyperemic T(mn). We also assessed insulin resistance by the homeostasis model assessment (HOMA) index. FFR was normal in all investigated arteries. CFR was significantly lower in diabetic vs. nondiabetic patients [median (interquartile range): 2.2 (1.4-3.2) vs. 4.1 (2.7-4.4); P = 0.02]. Basal T(mn) was lower in diabetic vs. nondiabetic subjects [median (interquartile range): 0.53 (0.25-0.71) vs. 0.64 (0.50-1.17); P = 0.04], while hyperemic T(mn) and IMR were similar. We found significant correlations at linear regression analysis between logCFR and the HOMA index (r(2) = 0.35; P = 0.0005) and between basal T(mn) and the HOMA index (r(2) = 0.44; P < 0.0001). In conclusion, compared with nondiabetic subjects, CFR is lower in patients with diabetes and epicardial coronary arteries free of severe stenosis, because of increased basal coronary flow, while hyperemic coronary flow is similar. Basal coronary flow relates to insulin resistance, suggesting a key role of cellular metabolism in the regulation of coronary blood flow.     

Characterizing momentum change and viscous loss of a hemodynamic endpoint in assessment of coronary lesions

Myocardial fractional flow reserve (FFR(myo)) and coronary flow reserve (CFR), measured with guidewire, and quantitative angiography (QA) are widely used in combination to distinguish ischemic from non-ischemic coronary stenoses. Recent studies have shown that simultaneous measurements of FFR(myo) and CFR are recommended to dissociate conduit epicardial coronary stenoses from distal resistance microvascular disease. In this study, a more comprehensive diagnostic parameter, named as lesion flow coefficient, c, is proposed. The coefficient, c, which accounts for mean pressure drop, Delta p, mean coronary flow, Q, and percentage area stenosis, can be used to assess the hemodynamic severity of a coronary artery stenoses. Importantly, the contribution of viscous loss and loss due to momentum change for several lesion sizes can be distinguished using c. FFR(myo), CFR and c were calculated for pre-angioplasty, intermediate and post-angioplasty epicardial lesions, without microvascular disease. While hyperemic c decreased from 0.65 for pre-angioplasty to 0.48 for post-angioplasty lesion with guidewire of size 0.35 mm, FFR(myo) increased from 0.52 to 0.87, and CFR increased from 1.72 to 3.45, respectively. Thus, reduced loss produced by momentum change due to lower percentage area stenosis decreased c. For post-angioplasty lesion, c decreased from 0.55 to 0.48 with the insertion of guidewire. Hence, increased viscous loss due to the presence of guidewire decreased c compared with a lesion without guidewire. Further, c showed a linear relationship with FFR(myo), CFR and percentage area stenosis for pre-angioplasty, intermediate and post-angioplasty lesion. These baseline values of c were developed from fluid dynamics fundamentals for focal lesions, and provided a single hemodynamic endpoint to evaluate coronary stenosis severity.     

Influence of hemodynamic conditions on fractional flow reserve: parametric analysis of underlying model

Pressure-based fractional flow reserve (FFR) is used clinically to evaluate the functional severity of a coronary stenosis, by predicting relative maximal coronary flow (Q(s)/Q(n)). It is considered to be independent of hemodynamic conditions, which seems unlikely because stenosis resistance is flow dependent. Using a resistive model of an epicardial stenosis (0-80% diameter reduction) in series with the coronary microcirculation at maximal vasodilation, we evaluated FFR for changes in coronary microvascular resistance (R(cor) = 0.2-0.6 mmHg. ml(-1). min), aortic pressure (P(a) = 70-130 mmHg), and coronary outflow pressure (P(b) = 0-15 mmHg). For a given stenosis, FFR increased with decreasing P(a) or increasing R(cor). The sensitivity of FFR to these hemodynamic changes was highest for stenoses of intermediate severity. For P(b) > 0, FFR progressively exceeded Q(s)/Q(n) with increasing stenosis severity unless P(b) was included in the calculation of FFR. Although the P(b)-corrected FFR equaled Q(s)/Q(n) for a given stenosis, both parameters remained equally dependent on hemodynamic conditions, through their direct relationship to both stenosis and coronary resistance.     

New method to measure coronary velocity and coronary flow reserve

Coronary flow reserve (CFR) is an important index of coronary microcirculatory function. The objective of this study was to validate the reproducibility and accuracy of intravascular conductance catheter-based method for measurements of baseline and hyperemic coronary flow velocity (and hence CFR). The absolute coronary blood velocity was determined by measuring the time of transit of a saline injection between two pairs of electrodes (known distance) on a conductance catheter during a routine saline injection without the need for reference flow. In vitro validation was made in the velocity range of 5 to 70 cm/s in reference to the volume collection method. In 10 swine, velocity measurements were compared with those from a flow probe in coronary arteries at different CFR attained by microsphere embolization. In vitro, the mean difference between the proposed method and volume collection was 0.7 ± 1.34 cm/s for steady flow and -0.77 ± 2.22 cm/s for pulsatile flow. The mean difference between duplicate measurements was 0 ± 1.4 cm/s. In in vivo experiments, the flow (product of velocity and lumen cross-sectional area that is also measured by the conductance catheter) was determined in both normal and stenotic vessels and the mean difference between the proposed method and flow probe was -1 ± 12 ml/min (flow ranged from 10 to 130 ml/min). For CFR, the mean difference between the two methods was 0.06 ± 0.28 (range of 1 to 3). Our results demonstrate the reproducibility and accuracy of velocity and CFR measurements with a conductance catheter by use of a standard saline injection. The ability of the combined measurement of coronary lumen area (as previously validated) and current velocity and CFR measurements provides an integrative diagnostic tool for interventional cardiology.     

Reduction of coronary flow reserve in patients with increased aortic stiffness

Aortic stiffness is thought to affect coronary blood flow, but little is known about its influence on coronary flow reserve (CFR). The objective of the present study was to investigate the relationship between aortic stiffness and CFR in matched patients with and without increased aortic stiffness. Stress transoesophageal echocardiography (TEE) as the CFR measurement and coronary angiography were performed in all cases. Increased aortic stiffness was defined if elastic modulus Ep > 680 mmHg. The following patient populations free of coronary artery disease were compared: 36 subjects with normal aortic distensibility and 19 age-, sex-, and risk factor-matched patients with increased aortic stiffness. CFR was significantly reduced in patients with increased aortic stiffness as compared with cases with normal aortic distensibility (2.64 +/- 1.16 vs. 2.12 +/- 0.58, p <0.01). Hyperaemic diastolic flow velocities were reduced in patients with increased aortic stiffness (129.5 +/- 36.6 cm/s vs. 102.1 +/- 39.8 cm/s, p <0.05). Negative correlations were found between Ep and hyperaemic diastolic coronary flow velocity (r = -0.41, p < 0.01) and CFR (r = -0.21, p < 0.05). CFR is reduced in patients with increased aortic stiffness and negative correlations exist between these functional parameters.     

Comparison of intima-media thickness and ophthalmic artery resistance index for assessing subclinical atherosclerosis in HIV-1-infected patients

Background

The determination of coronary flow reserve (CFR) is an essential concept at the moment of decision-making in ischemic heart disease. There are several direct and indirect tests to evaluate this parameter. In this sense, dobutamine stress echocardiography is one of the pharmacological method most commonly used worldwide. It has been previously demonstrated that CFR can be determined by this technique. Despite our wide experience with dobutamine stress echocardiography, we ignored the necessary heart rate to consider sufficient the test for the analysis of CFR. For this reason, our main goal was to determine the velocity of coronary flow in each stage of dobutamine stress echocardiography and the heart rate value necessary to double the baseline values of coronary flow velocity in the territory of the left anterior descending (LAD) coronary artery.

Methods

A total of 33 consecutive patients were analyzed. The patients included had low risk for coronary artery disease. All the participants underwent dobutamine stress echocardiography and coronary artery flow velocity was evaluated in the distal segment of LAD coronary artery using transthoracic color-Doppler echocardiography.

Results

The feasibility of determining CFR in the territory of the LAD during dobutamine stress echocardiography was high: 31/33 patients (94%). Mean CFR was 2.67 at de end of dobutamine test. There was an excellent concordance between delta HR (difference between baseline HR and maximum HR) and the increase in the CFR (correlation coefficient 0.84). In this sense, we found that when HR increased by 50 beats, CFR was ≥ 2 (CI 93-99.2%). In addition, 96.4% of patients reached a CFR ≥ 2 (IC 91.1 - 99%) at 75% of their predicted maximum heart rate.

Conclusions

We found that the feasibility of dobutamine stress echocardiography to determine CFR in the territory of the LAD coronary artery was high. In this study, it was necessary to achieve a difference of 50 bpm from baseline HR or at least 75% of the maximum predicted heart rate to consider sufficient the test for the analysis of CFR.     

Coronary flow reserve and heart failure in experimental coxsackievirus myocarditis. A transthoracic Doppler echocardiography study

The objective of this study was to apply transthoracic Doppler echocardiography (TTDE) in mice to study coronary flow reserve (CFR), an index of coronary microvascular function, in mild and severe forms of experimental viral myocarditis. Regarding methodology, BALB/c mice were infected with cardiotropic coxsackieviruses causing either a mild (Nancy strain) or a severe (Woodruff strain) myocarditis. Left ventricular dimensions, fractional shortening, and CFR (ratio of left coronary artery flow velocity during maximal adenosine-induced vasodilatation to rest) were measured by TTDE before infection and again 1 or 2 wk after infection. As a result, the resting flow velocity did not change after infection. In contrast, CFR reduced significantly 1 wk after infection with either virus variant [from 2.5 (SD 0.3) to 1.4 (SD 0.1) in severe and from 2.4 (SD 0.4) to 2.1 (SD 0.3) in mild myocarditis], being significantly lower in the severe than mild myocarditis. CFR remained low in severe myocarditis 2 wk after infection. Fractional shortening decreased to the same levels 1 wk after infection with either virus variant [from 0.54 (SD 0.02) to 0.43 (SD 0.03) in severe and from 0.51 (SD 0.03) to 0.44 (SD 0.02) in mild myocarditis, P < 0.05]. However, 2 wk after infection, mice with severe myocarditis had enlarged left ventricles and lower fractional shortening [0.31 (SD 0.03)] than mice with mild myocarditis [0.47 (SD 0.02), P < 0.01]. In conclusion, CFR measured with TTDE is reduced in coxsackievirus myocarditis in mice. Low CFR is associated with progressive heart failure, indicating that dysfunction of coronary microcirculation is a determinant of poor outcome in viral myocarditis.     

Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses

We studied the impact of systemic infusion of the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on coronary flow reserve (CFR) in patients with coronary artery disease (CAD). We have previously demonstrated that CFR to adenosine was significantly increased after systemic infusion of L-NMMA in normal volunteers but not in recently transplanted denervated hearts. At baseline, myocardial blood flow (MBF; ml x min(-1) x g(-1)) was measured at rest and during intravenous administration of adenosine (140 microg x kg(-1) x min(-1)) in 10 controls (47 +/- 5 yr) and 10 CAD patients (58 +/- 8 yr; P < 0.01 vs. controls) using positron emission tomography and (15)O-labeled water. Both MBF measurements were repeated during intravenous infusion of 10 mg/kg L-NMMA. CFR was calculated as the ratio of MBF during adenosine to MBF at rest. CFR was significantly higher in healthy volunteers than in CAD patients and increased significantly after L-NMMA in controls (4.00 +/- 1.10 to 6.15 +/- 1.35; P < 0.0001) and in patients, both in territories subtended by stenotic coronary arteries (>70% luminal diameter; 2.06 +/- 1.13 to 3.21 +/- 1.07; P < 0.01) and in remote segments (3.20 +/- 1.23 to 3.92 +/- 1.62; P < 0.05). In conclusion, CFR can be significantly increased in CAD by a systemic infusion of L-NMMA. Similarly to our previous findings in normal volunteers, this suggests that adenosine-induced hyperemia in CAD patients is constrained by a mechanism that can be relieved by systemic NOS inhibition with L-NMMA.     

Influence of zero flow pressure on fractional flow reserve

Fractional flow reserve (FFR) is a commonly used index to assess the functional severity of a coronary artery stenosis. It is conventionally calculated as the ratio of the pressure distal (P_d) and proximal (P_a) to the stenosis (FFR=P_d/P_a). We hypothesize that the presence of a zero flow pressure (P _zf), requires a modification of this equation. Using a dynamic hydraulic bench model of the coronary circulation, which allows one to incorporate an adjustable P _zf, we studied the relation between pressure-derived FFR=P_d/P_a, flow-derived true FFR_Q=Q_S/Q_N (=ratio of flow through a stenosed vessel to flow through a normal vessel), and the corrected pressure-derived FFR_C=(P_d–P_zf)/(P_a–P_zf) under physiological aortic pressures (70 mmHg, 90 mmHg, and 110 mmHg). Imposed P_zf values varied between 0 mmHg and 30 mmHg. FFR_C was in good agreement with FFR_Q, whereas FFR consistently overestimated FFR_Q. This overestimation increased when P_zf increased, or when P_a decreased, and could be as high as 56% (P_zf=30 mmHg and P_a=70 mmHg). According to our experimental study, calculating the corrected FFR_C instead of FFR, if P_zf is known, provides a physiologically more accurate evaluation of the functional severity of a coronary artery stenosis.     

Instantaneous wave-free ratio and fractional flow reserve in clinical practice

Objectives

To compare fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) measurements in an all-comer patient population with moderate coronary artery stenoses.

Background

Visual assessment of the severity of coronary artery stenoses is often discordant in moderate lesions. FFR allows reliable functional severity assessment in these cases but requires adenosine-induced hyperaemia with associated additional time, costs and side effects. The iFR is a hyperaemia-independent index.

Methods and results

Between November 2015 and February 2017, 356 consecutive patients were included in whom 515 coronary stenoses were measured using both iFR and FFR. Mean iFR and FFR were 0.90?±?0.09 and 0.86?±?0.08, respectively. iFR correlated well with FFR [r?=?0.75; p?<?0.001]. Receiver operating characteristic analysis identified an area under the curve of 0.92. An iFR-only strategy with a treatment cut-off ≤0.89 revealed a diagnostic classification agreement with the FFR-only strategy in 420 lesions (82%) with a sensitivity of 87%, a specificity of 80%, a positive predictive value of 56% and a negative predictive value of 96%.

Conclusions

Real-time iFR measurements have good negative predictive value compared to FFR, but moderate diagnostic accuracy (82%). It exposes fewer patients to adenosine, reduces procedure time and costs. Further prospective trials are needed to evaluate specific clinical settings, cut-off values and endpoints.

     

Coronary flow reserve in hypertrophic cardiomyopathy: relation with microvascular dysfunction and pathophysiological characteristics

Background. The decrease in coronary flow reserve (CFR) in hypertrophic cardiomyopathy (HCM) predisposes to myocardial ischaemia, systolic dysfunction and cardiac death. In this study we investigate to which extent haemodynamic, echocardiographic, and histological parameters contribute to the reduction of CFR. Methods. In ten HCM patients (mean age 44±14 years) and eight heart transplant (HTX) patients (mean age 51±6 years) CFR was calculated in the left anterior descending coronary artery. In all subjects haemodynamic, echocardiographic and histological parameters were assessed. The relationship between these variables and CFR was determined using linear regression analysis. Results. CFR was reduced in HCM compared with HTX patients (1.6±0.7 vs. 2.7±0.8, p<0.01). An increase in septal thickness (p<0.005), indexed left ventricular (LV) mass (p<0.005), LV end-diastolic pressure (p<0.001), LV outflow tract gradient (p<0.05) and a decrease in arteriolar lumen size (p<0.05) were all related to a reduction in CFR. Conclusion: In HCM patients haemodynamic (LV end-diastolic pressure, LV outflow tract gradient), echocardiographic (indexed LV mass) and histological (% luminal area of the arterioles) changes are responsible for a decrease in CFR. (Neth Heart J 2007;15:209-15.)     

Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve

Background

Some components of Nutraceuticals (NUT) such as red yeast rice and Morus alba have demonstrated positive effects on the endothelial function in hypercholesterolemic subjects. Our aim was to compare the effects of two different NUT combinations on cold pressure test (CPT) derived coronary flow reserve (CFR) assessed by transthoracic echo-Doppler.

Results

In a randomized, single-blind study, 28 consecutive patients with a variety of cardiovascular risk factors received NUT A (LopiGLIK®: berberine, red yeast rice powder, and leaf extract of Morus alba) or B (Armolipid Plus®: policosanol, red yeast rice, berberine, astaxantine, folic acidandcoenzyme Q10). An echo-Doppler exam with evaluation of CFR was performed at baseline, 2?h (acute test) and 30?days after daily NUT assumption. Blood sampling for metabolic profile and platelet aggregometry was performed at baseline and after 30?days of daily NUT assumption. CFR was not significantly modified at the acute test. After 30?days, CFR improved with NUT A (p <?0.0001), because of the increase of hyperemic flow velocity (p =?0.007), but not with NUT B. CFR was comparable between the two groups at baseline but became significantly higher after 30?days in NUT A (p <?0.02), with a higher CFR percent variation versus baseline (p =?0.008). Total cholesterol and LDL-cholesterol were reduced with both NUT A (p <?0.001 and p <?0.002, respectively) and B (both p <?0.02), whereas platelet aggregation did not significantly change. In the pooled group of patients, after adjusting for age and percent changes of systolic blood pressure, heart rate, LDL-cholesterol and glycemia, NUT A – but not NUT B - was independently associated with CFR changes (β?=?0.599, p =?0.003).

Conclusions

LopiGLIK® improved endothelial-derived CFR, independently of the beneficial effects exerted on the lipid profile. These findings can have clinical reflections on the prevention of age-related inflammatory diseases including coronary artery disease.

Trial registration

(NUTRENDO)″(ClinicalTrials.gov, NCT02969070).

     

The influence of artery wall curvature on the anatomical assessment of stenosis severity derived from fractional flow reserve: a computational fluid dynamics study

This study aims to investigate the influence of artery wall curvature on the anatomical assessment of stenosis severity and to identify a region of misinterpretation in the assessment of per cent area stenosis (AS) for functionally significant stenosis using fractional flow reserve (FFR) as standard. Five artery models of different per cent AS severity (70, 75, 80, 85 and 90%) were considered. For each per cent AS severity, the angle of curvature of the arterial wall varied from straight to an increasingly curved model (0°, 30°, 60°, 90° and 120°). Computational fluid dynamics was performed under transient physiologic hyperemic flow conditions to investigate the influence of artery wall curvature on the pressure drop and the FFR. The findings in this study may be useful in in vitro anatomical assessment of functionally significant stenosis. The FFR decreased with increasing stenosis severity for a given curvature of the artery wall. Moreover, a significant decrease in FFR was found between straight and curved models discussed for a given severity condition. These findings indicate that the curvature effect was included in the FFR assessment in contrast to minimum lumen area (MLA) or per cent AS assessment. The MLA or per cent AS assessment may lead to underestimation of stenosis severity. From this numerical study, an uncertainty region could be evaluated using the clinical FFR cutoff value of 0.8. This value was observed at 81.98 and 79.10% AS for arteries with curvature angles of 0° and 120° respectively. In conclusion, the curvature of the artery should not be neglected in in vitro anatomical assessment.     

Minimal effect of collateral flow on coronary microvascular resistance in the presence of intermediate and noncritical coronary stenoses

Depending on stenosis severity, collateral flow can be a confounding factor in the determination of coronary hyperemic microvascular resistance (HMR). Under certain assumptions, the calculation of HMR can be corrected for collateral flow by incorporating the wedge pressure (P(w)) in the calculation. However, although P(w) > 25 mmHg is indicative of collateral flow, P(w) does in part also reflect myocardial wall stress neglected in the assumptions. Therefore, the aim of this study was to establish whether adjusting HMR by P(w) is pertinent for a diagnostically relevant range of stenosis severities as expressed by fractional flow reserve (FFR). Accordingly, intracoronary pressure and Doppler flow velocity were measured a total of 95 times in 29 patients distal to a coronary stenosis before and after stepwise percutaneous coronary intervention. HMR was calculated without (HMR) and with P(w)-based adjustment for collateral flow (HMR(C)). FFR ranged from 0.3 to 1. HMR varied between 1 and 5 and HMR(C) between 0.5 and 4.2 mmHg·cm(-1)·s. HMR was about 37% higher than HMR(C) for stenoses with FFR < 0.6, but for FFR > 0.8, the relative difference was reduced to 4.4 ± 3.4%. In the diagnostically relevant range of FFR between 0.6 and 0.8, this difference was 16.5 ± 10.4%. In conclusion, P(w)-based adjustment likely overestimates the effect of potential collateral flow and is not needed for the assessment of coronary HMR in the presence of a flow-limiting stenosis characterized by FFR between 0.6 and 0.8 or for nonsignificant lesions.