Quantification of absolute coronary flow reserve and relative fractional flow reserve in a swine animal model using angiographic image data

Coronary flow reserve (CFR) and fractional flow reserve (FFR) are important physiological indexes for coronary disease. The purpose of this study was to validate the CFR and FFR measurement techniques using only angiographic image data. Fifteen swine were instrumented with an ultrasound flow probe on the left anterior descending artery (LAD). Microspheres were gradually injected into the LAD to create microvascular disruption. An occluder was used to produce stenosis. Contrast material injections were made into the left coronary artery during image acquisition. Volumetric blood flow from the flow probe (Q(q)) was continuously recorded. Angiography-based blood flow (Q(a)) was calculated by using a time-density curve based on the first-pass analysis technique. Flow probe-based CFR (CFR(q)) and angiography-based CFR (CFR(a)) were calculated as the ratio of hyperemic to baseline flow using Q(q) and Q(a), respectively. Relative angiographic FFR (relative FFR(a)) was calculated as the ratio of the normalized Q(a) in LAD to the left circumflex artery (LC(X)) during hyperemia. Flow probe-based FFR (FFR(q)) was measured from the ratio of hyperemic flow with and without disease. CFR(a) showed a strong correlation with the gold standard CFR(q) (CFR(a) = 0.91 CFR(q) + 0.30; r = 0.90; P < 0.0001). Relative FFR(a) correlated linearly with FFR(q) (relative FFR(a) = 0.86 FFR(q) + 0.05; r = 0.90; P < 0.0001). The quantification of CFR and relative FFR(a) using angiographic image data was validated in a swine model. This angiographic technique can potentially be used for coronary physiological assessment during routine cardiac catheterization.     

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.     

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.     

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.     

Effects of diagnostic guidewire catheter presence on translesional hemodynamic measurements across significant coronary artery stenoses

This study gains insight on the nature of flow blockage effects of small guidewire catheter sensors in measuring mean trans-stenotic pressure gradients Deltap across significant coronary artery stenoses. Detailed pulsatile hemodynamic computations were made in conjunction with previously reported clinical data in a group of patients with clinically significant coronary lesions before angioplasty. Results of this study ascertain changes in hemodynamic conditions due to the insertion of a guidewire catheter (di=0.46 mm) across the lesions used to directly determine the mean pressure gradient (Deltap) and fall in distal mean coronary pressure (pr). For the 32 patient group of Wilson et al. [1988] (minimal lesion diameter dm=0.95 mm; 90% mean area stenosis; proximal measured coronary flow reserve (CFR) of 2.3 in the abnormal range) the diameter ratio of guidewire catheter to minimal lesion was 0.48, causing a tighter "artifactual" mean area stenosis of 92.1%. The results of the computations indicated a significant shift in the Deltap-Q relation due to guidewire induced increases in flow resistances (R=Deltap/Q) of 110% for hyperemic flow, a 35% blockage in hyperemic flow (Qh) and a phase shift of the coronary flow waveform to systolic predominance. These alterations in flow resulted in a fall in distal mean coronary pressure (at lower mean flow rates) below the patho-physiological range of prh approximately 55 mmHg, which is known to cause ischemia in the subendocardium (Brown et al. [1984]) and coincides with symptomatic angina. Transient wall shear stress levels in the narrow throat region (with flow blockage) were of the order of levels during hyperemic conditions for patho-physiological flow. In the separated flow region along the distal vessel wall, vortical flow cells formed periodically during the systolic phase when instantaneous Reynolds numbers Ree(t) exceeded about 110. For patho-physiological flow without the presence of the guidewire these vortical flow cells were much stronger than in the more viscous flow regime with the guidewire present. The non-dimensional pressure data given in tabular form may be useful in interpretation of guidewire measurements done clinically for lesions of similar geometry and severity.     

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.     

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.     

Deferring angioplasty in intermediate coronary lesions based on coronary flow criteria is safe: comparison of a deferred group to an intervention group

The decision for revascularization in patients with intermediate coronary lesions remains a challenging topic, particularly when objective data of reversible ischemia are lacking. In some of the patients, coronary revascularization is performed or deferred without definitive evidence on the clinical significance of the coronary stenosis. We investigated the usefulness of coronary flow reserve (CFR) measurements in 28 patients with intermediate coronary lesions. We compared 20 patients who underwent angioplasty based on Doppler-wire-derived CFR with 8 patients for whom angioplasty was deferred (diameter stenosis of 50.7 +/- 2.0% versus 46.5 +/- 3.1%, P < 0.0001 and CFR of 1.80 +/- 0.32 versus 2.65 +/- 0.11, P = 0.002, respectively). Angioplasty resulted in normalization of the CFR to 2.57 +/- 0.53 (P < 0.0001, versus the baseline value). During a follow-up period of 58.1 weeks (range 23-149 weeks), eight patients in the revascularization group were readmitted to the hospital, one of them with a myocardial infarction in the territory of the target vessel, compared with only one admission in the deferred group. Target-vessel revascularization was performed in three patients (a fourth patient declined it) in the former group, compared with only one in the latter. Symptomatic improvement or no change in clinical status was observed in the majority of patients in both groups (90% in the revascularization group and 87.5% in the deferred group). We conclude that in a selected group of patients with intermediate coronary lesions, measurement of CFR may be a useful tool in determining the need for revascularization based on its physiologic significance. Importantly, deferring PTCA in patients with intermediate lesions and normal CFR values seems to be safe.     

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.     

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.     

Physiological flow analysis in significant human coronary artery stenoses

To evaluate the local hemodynamics in flow limiting coronary lesions, computational hemodynamics was applied to a group of patients previously reported by Wilson et al. (1988) with representative pre-angioplasty stenosis geometry (minimal lesion size d(m)=0.95 mm; 68% mean diameter stenosis) and with measured values of coronary flow reserve (CFR) in the abnormal range (2.3+/-0.1). The computations were at mean flow rates (Q) of 50, 75 and 100 ml/min (the limit of our converged calculations). Computed mean pressure drops Deltap were approximately 9 mmHg for basal flow (50 ml/min), approximately 27 mmHg for elevated flow (100 ml/min) and increased to an extrapolated value of approximately 34 mmHg for hyperemic flow (115 ml/min), which led to a distal mean coronary pressure p(rh) of approximately 55 mmHg, a level known to cause ischemia in the subendocardium (Brown et al., 1984), and consistent with the occurrence of angina in the patients. Relatively high levels of wall shear stress were computed in the narrow throat region and ranged from about 600 to 1500 dyn/cm(2), with periodic (phase shifted) peak systolic values of about 3500 dyn/cm(2). In the distal vessel, the interaction between the separated shear layer wave, convected downstream by the core flow, and the wall shear layer flow, led to the formation of vortical flow cells along the distal vessel wall during the systolic phase where Reynolds numbers Re(e)(t) were higher. During the phasic vortical mode observed at both basal and elevated mean flow rates, wide variations in distal wall shear stress occurred, distal transmural pressures were depressed below throat levels, and pressure recovery was larger farther along the distal vessel. Along the constriction (convergent) and throat segments of the lesion the pulsatile flow field was principally quasi-steady before flow separation occurred. The flow regimes were complex in the narrow mean flow Reynolds number range Re(e)=100-230 and a frequency parameter of alphae=2.25. The shear layer flow disturbances diminished in strength due to viscous damping along the distal vessel at these relatively low values of Re(e), typical of flow through diseased epicardial coronary vessels. The distal hyperemic flow field was likely to be in an early stage of turbulent flow development during the peak systolic phase.     

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).

     

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.     

Effect of chronic cocaine administration and cocaine withdrawal on coronary flow rate and heart rate responses to epinephrine and cocaine in isolated perfused rat hearts

The acute dose-dependent effects of epinephrine and cocaine on heart rate and coronary flow rate (CFR) were examined in isolated, perfused (Langendorff) rat hearts from animals: i) pretreated with daily cocaine injections (20 mg/kg/day) for 8 weeks; ii) after 2-day withdrawal from 8-week cocaine pretreatment; iii) vehicle-treated controls. Chronic cocaine (CC) hearts were significantly less sensitive to the chronotropic effects of epinephrine than control (C) or withdrawal (CW) hearts. CW hearts exhibited significantly higher heart rates in response to epinephrine than C and CC hearts. Epinephrine alone (2.5 x 10(-7) M) decreased CFR 11% (C), 9%(CC), 14%(CW) from respective baseline levels. Cocaine alone had no significant effect on CFR in C hearts but produced slight dose-dependent decrements in CFR in CC and particularly CW hearts at higher doses. Cocaine plus epinephrine markedly decreased CFR in all groups, particularly in CW hearts. The results indicate that chronic daily cocaine administration produces a functional tolerance of the heart to the chronotropic actions of epinephrine but a 2-day withdrawal from chronic cocaine results in a rebound supersensitivity to adrenergic stimulation and cocaine's sympathomimetic effects. In addition, cocaine produces only minor decrements in coronary flow in the rat heart, while cocaine acts synergisticallly with epinephrine to produce a marked decrease in CFR.     

Assessment of coronary flow reserve in nuclear cardiology

The coronary flow reserve is a quantitative parameter defined by the ratio maximal myocardial blood flow to rest myocardial blood flow, which allows to give functional information on the whole coronary arterial tree, integrating both epicardial arteries and microcirculatory. The coronary flow reserve is a powerful tool to guide therapy and to assess prognosis. Exploratory tools, initially limited to experimental invasive techniques, have evolved over the last 10 years, allowing to envisage its use in daily clinical practice. This article reviews the pathophysiology of the coronary flow reserve and the various invasive and non-invasive exploration tools available to practitioners, integrating them into clinical practice.     

A single center experience with the newly designed R Stent in small coronary vessels

BACKGROUND: Over the past 10 years stents have been used more frequently for the treatment of de novo coronary artery stenosis. Initally these devices were used primarily in coronary arteries with diameters ranging from 3.0 to 4.0 mm. Traditionally, coronary arteries less than 3.0 mm in diameter were treated with only balloon angioplasty, due to the unavailablity of flexible, low profile, small diameter stents. In the past three years, many stents have been designed to be implanted in small coronary arteries. OBJECTIVE: The objective of this study was to evaluate the safety and feasiblity of the R Stent in patients with coronary lesions located in coronary arteries with a reference diameter 2.5-3.0 mm. METHODS AND RESULTS: Between November 1998 and September 1999, 32 patients with stable (37%) and unstable (63%) angina treated with the R Stent were included in this study. The treated lesions were in the right coronary artery (RCA) (n = 13), left cirumflex coronary artery (LCX) (n = 10), and left anterior descending coronary artery (LAD) (n = 9). Of these lesions thirteen were anatomically complex. Stent deployment was successful in 97% with one crossing failure in a patient with a vessel tortuosity of greater than 75 degrees of the circumflex artery. No post-procedual major adverse cardiac and cerebrovascular event (MACCE) occurred within 30 days of stent implantation. After the procedure, patients were scheduled for a two-week telephone follow-up and a one-month clinical evaluation. At 30 days, only one patient (3%) experienced the recurrence of angina Canadian cardiovascular society classification ((CCS) Class 2). All other patients were event and angina free. CONCLUSION: This first clinical experience in patients with small vessel disease shows that the use of the R stent is safe and feasible with low rates of acute stent thrombosis.     

Noninvasive determination of upper airway resistance and flow limitation.

We have shown that a polynomial equation, FP = AP3 + BP2 + CP + D, where F is flow and P is pressure, can accurately determine the presence of inspiratory flow limitation (IFL). This equation requires the invasive measurement of supraglottic pressure. We hypothesized that a modification of the equation that substitutes time for pressure would be accurate for the detection of IFL and allow for the noninvasive measurement of upper airway resistance. The modified equation is Ft = At3 + Bt2 + Ct + D, where F is flow and t is time from the onset of inspiration. To test our hypotheses, data analysis was performed as follows on 440 randomly chosen breaths from 18 subjects. First, we performed linear regression and determined that there is a linear relationship between pressure and time in the upper airway (R2 0.96 +/- 0.05, slope 0.96 +/- 0.06), indicating that time can be a surrogate for pressure. Second, we performed curve fitting and found that polynomial equation accurately predicts the relationship between flow and time in the upper airway (R2 0.93 +/- 0.12, error fit 0.02 +/- 0.08). Third, we performed a sensitivity-specificity analysis comparing the mathematical determination of IFL to manual determination using a pressure-flow loop. Mathematical determination had both high sensitivity (96%) and specificity (99%). Fourth, we calculated the upper airway resistance using the polynomial equation and compared the measurement to the manually determined upper airway resistance (also from a pressure-flow loop) using Bland-Altman analysis. Mean difference between calculated and measured upper airway resistance was 0.0 cmH2O x l(-1) x s(-1) (95% confidence interval -0.2, 0.2) with upper and lower limits of agreement of 2.8 cmH2O x l(-1) x s(-1) and -2.8 cmH2O x l(-1) x s(-1). We conclude that a polynomial equation can be used to model the flow-time relationship, allowing for the objective and accurate determination of upper airway resistance and the presence of IFL.