Simultaneous intracoronary velocity- and pressure-derived assessment of adenosine-induced collateral hemodynamics in patients with one- to two-vessel coronary artery disease

OBJECTIVES

The purpose of this investigation in patients with poorly and well developed coronary collaterals was to assess the influence of collateral and collateral adjacent vascular resistances and, in part, a stenotic lesion of the collateral supplying vessel on the hemodynamic collateral responses to adenosine.

BACKGROUND

In humans, little is known about the functional behavior of the coronary collateral circulation.

METHODS

In 50 patients with one- and two-vessel coronary artery disease (CAD) undergoing percutaneous transluminal coronary angioplasty (PTCA), collateral flow index (CFI, no unit) changes and vascular resistance index (R, cm/mm Hg) changes of the collateral (R_coll) and the distal collateral receiving (R₄) vessel in response to adenosine (140 μg/min/kg IV) were measured by intracoronary (i.c.) Doppler and pressure guidewires. The variables were determined at baseline and during adenosine in patients with poor (angiographic collateral degree before PTCA <2 of 0 to 3) and good coronary collaterals.

RESULTS

Pressure-derived CFI (CFI_p) decreased under adenosine in patients with poor collaterals, and it increased in the group with good collaterals. There were inverse correlations between the adenosine-induced change in CFI_p and the change in R_coll (r = 0.61, p = 0.0001). In the group with good, but not with poor collaterals, there was also a significant correlation between CFI_p increase and the decrease in R₄, between the severity of the contralateral stenosis and CFI_p augmentation and among the left versus right coronary artery as ipsilateral vessel and CFI_p change.

CONCLUSIONS

Overall, patients with well, versus poorly developed coronary collaterals do better regarding the capacity to increase collateral flow in response to adenosine. In patients with good, but not poor, collaterals, an adenosine-induced collateral flow increase depends on the ipsilateral distal vascular resistance decrease, but is also directly influenced by the severity of a contralateral stenosis and probably by the size of the collateralized vascular bed.     

Collateral and collateral-adjacent hyperemic vascular resistance changes and the ipsilateral coronary flow reserve. Documentation of a mechanism causing coronary steal in patients with coronary artery disease

OBJECTIVES: The goal of this clinical study was to assess the influence of hyperemic ipsilateral, collateral and contralateral vascular resistance changes on the coronary flow velocity reserve (CFVR) of the collateral-receiving (i.e. ipsilateral) artery, and to test the validity of a model describing the development of collateral steal. METHODS: In 20 patients with one- to two-vessel coronary artery disease (CAD) undergoing angioplasty of one stenotic lesion, adenosine induced intracoronary (i.c.) CFVR during vessel patency was measured using a Doppler guidewire. During stenosis occlusion, simultaneous i.c. distal ipsilateral flow velocity and pressure (P(occl), using a pressure guidewire) as well as contralateral flow velocity measurements via a third i.c. wire were performed before and during intravenous adenosine. From those measurements and simultaneous mean aortic pressure (P(ao)), a collateral flow index (CFI), and the ipsilateral, collateral, and contralateral vascular resistance index (R(ipsi), R(coll), R(contra)) were calculated. The study population was subdivided into groups with CFI<0.15 and with CFI> or =0.15. RESULTS: The percentage-diameter coronary artery stenosis (%-S) to be dilated was similar in the two groups: 78+/-10% versus 82+/-12% (NS). CFVR was not associated with %-S. In the group with CFI> or =0.15 but not with CFI<0.15, CFVR was directly and inversely associated with R(coll) and R(contra), respectively. CONCLUSIONS: A hemodynamic interaction between adjacent vascular territories can be documented in patients with CAD and well developed collaterals among those regions. The CFVR of a collateralized region may, thus, be more dependent on hyperemic vascular resistance changes of the collateral and collateral-supplying area than on the ipsilateral stenosis severity, and may even fall below 1.     

Physiologically assessed coronary collateral flow and adverse cardiac ischemic events: a follow-up study in 403 patients with coronary artery disease

OBJECTIVES: We sought to evaluate whether coronary collateral flow is clinically relevant for future cardiac ischemic events. BACKGROUND: The link between good collateral supply related to less myocardial damage and fewer cardiac events has not been established prospectively beyond doubt. METHODS: In 403 patients with stable angina pectoris undergoing percutaneous transluminal coronary angioplasty (PTCA) and quantitative collateral assessment, the occurrence of major adverse cardiac events ([MACE] cardiac death, myocardial infarction, unstable angina pectoris) and stable angina pectoris was monitored during follow-up. Collateral flow index (CFI) was determined using intracoronary pressure or Doppler guidewires. Mean aortic ([P(ao)] mm Hg) and distal coronary artery occlusive pressure ([P(occl)] mm Hg) during balloon angioplasty (PTCA), or distal coronary flow velocity time integral during ([V(occl)] cm) and after ([V(?-occl)] cm) PTCA were measured continuously. Pressure-derived CFI was calculated as follows: (P(occl) - 5)/(P(ao) - 5). Doppler-derived CFI: V(occl)/V(?-occl). Patients were subdivided into a group with well (CFI > or = 0.25) and poorly developed collaterals (CFI < 0.25). RESULTS: Average follow-up was 94 +/- 56 (15 to 202) weeks. There were 134 patients with CFI >or =0.25 (61 +/- 11 years) and 269 with CFI <0.25 (61 +/- 10 years). The overall cardiac ischemic event rate (MACE and stable angina pectoris) during follow-up was 23% in patients with CFI > or =0.25 and 20% in patients with CFI <0.25 (p = NS). However, only 2.2% of patients with good collateral flow suffered a major cardiac ischemic event, compared with 9.0% among patients with poorly developed collaterals (p = 0.01). The incidence of stable angina pectoris was significantly higher in patients with well developed collaterals than in those with poorly developed collaterals (21% vs. 12%; p = 0.01). CONCLUSIONS: In this relatively large population with chronic stable coronary artery disease undergoing quantitative collateral measurement, the beneficial impact of well developed collateral vessels on the occurrence of future major cardiac ischemic events is clearly demonstrated.     

Coronary flow reserve in the contralateral artery increases after successful coronary angioplasty in patients with spontaneously visible collateral vessels

Objective—To test the hypothesis that coronary flow reserve could increase in the angiographically normal contralateral artery after successful coronary angioplasty of an ipsilateral coronary artery.
Design—Coronary flow reserve was estimated using a Doppler flow guide wire, by giving intracoronary adenosine in the contralateral artery, before and 15 minutes after the end of angioplasty.
Setting—Tertiary referral centre.
Patients—31 patients, mean (SD) age 56 (11) years, with stable angina and single vessel disease, undergoing angioplasty of the right coronary or the left anterior descending artery.
Results—In the contralateral artery baseline average peak velocity was 21 (9) cm/s before angioplasty and decreased to 12 (6) cm/s after (p < 0.005), while hyperaemic average peak velocity was 47 (19) cm/s before and decreased to 34 (15) cm/s after (p < 0.005). However, coronary flow reserve in the contralateral artery was 2.4 (0.7) before angioplasty and increased to 2.9 (0.6) after (p < 0.05). The contralateral coronary flow reserve after angioplasty increased by 0.8 (0.4) in 11 patients with visible collaterals before angioplasty and by 0.3 (0.6) in the remaining patients without visible collaterals (p < 0.05). Blood pressure and heart rate were unchanged after the procedure.
Conclusions—Coronary flow reserve in an angiographically normal contralateral artery increases after successful coronary angioplasty of the ipsilateral artery in patients with spontaneously visible collateral vessels before the procedure.

Keywords: coronary flow reserve; contralateral coronary artery; angioplasty     

Coronary collateral quantitation in patients with coronary artery disease using intravascular flow velocity or pressure measurements

Objectives. This study evaluated two methods for the quantitative measurement of collaterals using intracoronary (IC) blood flow velocity or pressure measurements.Background. The extent of myocardial necrosis after coronary artery occlusion is substantially influenced by the collateral circulation. So far, qualitative methods have been available to assess the human coronary collateral circulation, thus restraining the conclusive investigation of, for example, therapies to promote collateral development.Methods. Fifty-one patients with a coronary artery stenosis to be treated by percutaneous transluminal coronary angioplasty (PTCA) were investigated using IC PTCA guidewire-based Doppler and pressure sensors positioned distal to the stenosis. Simultaneous measurements of aortic pressure, IC velocity and pressure distal to the stenosis during and after PTCA provided the variables for calculating collateral flow indices (CFI_vand CFI_p) that express collateral flow as a fraction of flow via the patent vessel. Both CFI_vand CFI_pwere compared with conventional methods for collateral assessment, among them ST-segment changes >1 mm on IC and surface electrocardiogram (ECG) at PTCA. Also, CFI_vand CFI_pwere compared with each other.Results. In 11 patients without ECG signs of ischemia during PTCA (sufficient collaterals), relative collateral flow amounted to 46% as determined by Doppler and pressure wire. Patients with insufficient collaterals (n = 40) had relative collateral flow values of 18%. Using a threshold of CFI = 30%, sufficient and insufficient collaterals could be diagnosed with 100% sensitivity and 93% specificity by IC Doppler, and 75% sensitivity and 92% specificity by IC pressure measurements. The agreement between Doppler and pressure measurements was good: CFI_v= 0.08 + 0.8 CFI_p, r = 0.80, p = 0.0001.Conclusions. Intracoronary flow velocity or pressure measurements during routine PTCA represent an accurate and, at last, quantitative method for assessing the coronary collateral circulation in humans.     

Frequency distribution of collateral flow and factors influencing collateral channel development : Functional collateral channel measurement in 450 patients with coronary artery disease

OBJECTIVES

We sought to determine the pathogenetic predictors of collateral channels in a large cohort of patients with coronary artery disease (CAD).

BACKGROUND

The frequency distribution of collateral flow in patients with CAD is unknown. Only small qualitative studies have investigated which factors influence the development of collateral channels.

METHODS

In 450 patients with one- to three-vessel CAD undergoing percutaneous transluminal coronary angioplasty (PTCA), collateral flow was measured. A collateral flow index (CFI; no unit) expressing collateral flow relative to normal anterograde flow was determined using coronary wedge pressure or Doppler measurements through sensor-tipped PTCA guide wires. Frequency distribution analysis of CFI and univariate and multivariate analyses of 32 factors, including gender, age, patient history, cardiovascular risk factors, medication and coronary angiographic data, were performed.

RESULTS

Two-thirds of the patients had a CFI <0.25 and 40% of patients had a CFI <0.15, but only 10% of the patients had a recruitable CFI ≥0.4. By univariate analysis, the following were predictors of CFI ≥0.25: high levels of high-density lipoprotein cholesterol, the absence of previous non–Q-wave myocardial infarction, angina pectoris during an exercise test, angiographic indicators of severe CAD and the left circumflex or right coronary artery as the collateral-receiving vessel. Percent diameter stenosis of the lesion undergoing PTCA was the only independent predictor of a high CFI.

CONCLUSIONS

This large clinical study of patients with CAD in whom collateral flow was quantitatively assessed reveals that two-thirds of the patients do not have enough collateral flow to prevent myocardial ischemia during coronary occlusion, and that coronary lesion severity is the only independent pathogenetic variable related to collateral flow.     

Quantitatively assessed coronary collateral circulation and restenosis following percutaneous revascularization.

AIMS: A high degree of collateral supply to a vascular area where a percutaneous transluminal coronary angioplasty (PTCA) has been performed represents a haemodynamic force competing with the antegrade flow through the dilated lesion. Therefore, our purpose was to determine whether patients with restenosis following PTCA have a higher collateral flow to the recipient vessel than patients without restenosis. METHODS AND RESULTS: In 200 consecutive PTCA patients, an intracoronary pressure-derived collateral flow index (CFI) was determined quantitatively during balloon occlusion, using simultaneous measurements of the mean aortic pressure (P(ao)) and of the intracoronary pressure distal to the occluded stenosis (P(occl)), as well as the estimated central venous pressure (CVP=5 mmHg): CFI=(P(occl)-CVP)/(P(ao)-CVP). Sixty-four patients had an angiographic follow-up examination after at least 2 months, and were subdivided into patients with restenosis (>50% diameter stenosis, n=34) and patients without restenosis (n=30). Patients with restenosis had a significantly higher collateral flow index at the initial coronary angiography than patients without restenosis (0.26 +/- 0.14 vs 0.12 +/- 0.09; P<0.0001). CONCLUSIONS: Patients with restenosis after PTCA show a more extended collateral supply to this recipient area than patients without restenosis. Well developed collaterals to a revascularized region are a risk factor for restenosis of the treated lesion.     

Prediction of restenosis after percutaneous transluminal coronary angioplasty using coronary flow reserve. Kansai Doppler Guide Wire Study Group

This multi-center prospective study attempted to predict restenosis after percutaneous transluminal coronary angioplasty(PTCA) using coronary flow reserve. Intracoronary blood flow velocity was measured in 47 patients(37 males, 10 females, mean age 66 +/- 9 years) with a Doppler guide wire, following successful PTCA. Twenty-four patients had prior myocardial infarction. After successful PTCA, a Doppler guide wire was placed at the distal portion of the target lesion, and coronary blood flow velocity was measured before and during intravenous administration of adenosine triphosphate. Follow-up coronary angiography was performed 154 +/- 69 days after PTCA, and the diameter stenosis of the target lesion was measured using quantitative coronary angiography. Follow-up angiography showed restenosis in 13 patients(28%). Sensitivity and specificity for predicting restenosis were low(50%, 45%, respectively) with a post-PTCA% diameter stenosis cut-off point of 27%. Sensitivity and specificity were 67% and 61% with a minimal lumen diameter cut-off of 1.8 mm. The reference coronary artery diameter(cut-off point 2.5 mm) was better for predicting restenosis(sensitivity 78% and specificity 76%). Sensitivity and specificity were 62% and 67%, respectively, using coronary flow reserve(cut-off point 2.0). The restenosis rate of patients with a reference diameter of more than 2.5 mm was 10%, but 54% for those with less than 2.5 mm(p < 0.05). In patients with a reference diameter of less than 2.5 mm, coronary flow reserve was useful for predicting restenosis(cut-off point 1.9, sensitivity 71% and specificity 83%). Coronary flow reserve is useful for predicting restenosis after PTCA, when combined with reference coronary artery diameter.     

The effect of rapid decreases of blood pressure by different mechanisms on coronary flow and flow reserve in normal coronary arteries

BACKGROUND: Changes in mean blood pressure (MBP) alter coronary blood flow (CBF). We evaluated the acute effects of three hypotensive medications on CBF parameters in angiographically normal coronary arteries. METHODS: We performed CBF measurements using the Doppler wire at rest and during hyperemia produced by intracoronary adenosine (18 microg) as follows: 1) in the normal left circumflex coronary artery in 20 patients with coronary artery disease (measurements were performed without drugs, and after intravenous infusion of nitroprusside [0.5 to 2 microg/kg/min] and nitroglycerin [10 to 90 microg/min]; drugs were titrated to decrease MBP 20% to 25% below the control values, and heart rate was held constant using right atrial pacing); and 2) in the normal left anterior descending coronary artery in 19 patients without coronary artery disease (measurements were performed before and after intravenous clonidine infusion [150 microg in 5 min]; time-averaged peak velocity [APV], CBF, and coronary flow reserve [CFR] were measured). RESULTS: Similar decreases in MBP were obtained in the two patient groups. Lumen diameter at the site of Doppler measurements increased after all medications (P <.005), whereas CBF did not change significantly. The CFR decreased after nitroprusside (1.79 +/- 0.48 v 2.54 +/- 0.45, P=.000), did not change significantly after nitroglycerin (2.74 +/- 0.43 v 2.54 +/- 0.45, P =.097), and increased after clonidine (3.12 +/- 0.70 v 2.76 +/- 0.75, P =.006). CONCLUSIONS: In normal coronary arteries the infusion of three hypotensive medications to produce the same decreases in MBP is associated with different effects on CFR (increase with clonidine, decrease with nitroprusside, and no change with nitroglycerin).     

Coronary blood flow velocity during percutaneous transluminal coronary angioplasty as a guide for assessment of the functional result

To investigate the clinical usefulness of intracoronary Doppler recordings during percutaneous transluminal coronary angioplasty (PTCA), the changes of intracoronary blood flow velocity during PTCA were assessed in 20 patients with single proximal coronary stenosis, using a Doppler probe end-mounted on the tip of a PTCA catheter. A mean of 4 inflations was performed in each patient. Intracoronary velocities were measured before and after each inflation and during peak reactive hyperemia after each transluminal occlusion. Quantitative analysis of the coronary stenosis was assessed before and after PTCA, and the dilatation resulted in an increase in minimal luminal cross-sectional area from 1.1 +/- 0.8 to 2.7 +/- 1.2 mm2. A gradual and significant improvement in velocities was observed after the first 3 dilatations, but in 15 of the 20 patients the resting and hyperemic velocities were not affected by the fourth dilatation. Coronary flow reserve measured during reactive hyperemia after the last dilatation with the PTCA catheter across the lesion was 1.9. This value of coronary flow reserve is compatible with the residual stenosis measured after PTCA when corrected for the presence of the Doppler balloon catheter (0.68 mm2). This application of the Doppler technique may provide a new method of on-line functional monitoring of the PTCA procedure in individual patients, but does not yet allow an accurate prediction of the change in coronary geometry brought about by PTCA.     

Effects of smoking on coronary blood flow velocity and coronary flow reserve assessed by transthoracic Doppler echocardiography

BACKGROUND: Smoking is a well-known risk factor for cardiovascular disease. Coronary blood flow velocity (CFV) can be measured directly with transthoracic Doppler echocardiography (TTDE) which is conducted immediately after smoking. PURPOSE: The purpose of this study was to evaluate the chronic and acute effects of smoking on coronary blood flow and coronary flow reserve (CFR) by the use of TTDE. METHODS: Healthy volunteers (11 smokers and 9 nonsmokers) with a mean age of 27 +/- 3 years were included. Smoking was abstained for at least 4 hours before the study. CFV was measured at the distal left anterior descending coronary artery by TTDE at baseline and during intravenous adenosine infusion (140 microg/kg per minute) in all participants. For smokers, CFV was measured immediately after consecutively smoking two cigarettes and during adenosine infusion. RESULTS: CFR and coronary vascular resistance index (CVRI) showed no significant difference between nonsmokers and smokers (CFR: 3.5 +/- 0.8 vs 3.6 +/- 0.6, P = ns, CVRI: 0.28 vs 0.28, P = ns) at baseline. CFR significantly decreased (3.6 +/- 0.6 to 2.8 +/- 0.7, P = 0.008) and CVRI markedly increased (0.28 to 0.35, P = 0.012) after smoking. CONCLUSION: After 4 hours of abstinence from smoking, CFR and CVRI in smokers were similar to those of nonsmokers. However, consecutively smoking two cigarettes acutely reduced CFR and increased CVRI. These findings suggested that smoking could reduce coronary blood flow immediately, even in healthy people.     

Recruitable collateral blood flow index predicts coronary instent restenosis after percutaneous coronary intervention.

AIMS: Collateral flow may influence long-term results after percutaneous coronary intervention (PCI) because of haemodynamic forces compete with the antegrade flow through the dilated lesion. The aim of the study was to assess the influence of recruitable collateral blood flow on restenosis in patients undergoing PCI with bare metal stents and using optimal antithrombotic treatment. METHODS AND RESULTS: In 95 patients, 95 de novo lesions were treated with PCI and a bare metal stent. Fractional flow reserve (FFR) at maximum hyperaemia induced by intravenous adenosine was determined. The pressure-derived collateral flow index (CFI) was determined as (P(w)-P(cvp))/(P(a)-P(cvp)), where P(w) represents coronary wedge pressure, P(cvp) central venous pressure, and P(a) mean aortic blood pressure. Both were measured during transient coronary occlusion by a balloon inflation of 30 s. Pre-interventional FFR (0.65 +/- 0.20) correlated inversely with the CFI (0.18 +/- 0.11), r =- 0.356, P < 0.001. After 9 months, binary angiographic restenosis (>/=50% diameter stenosis) was seen in 29.1%. Compared to patients with poorly developed collaterals (CFI < 0.25), patients with well-developed collaterals (CFI >/= 0.25) had a lower pre-interventional FFR (0.50 +/- 0.14 vs. 0.72 +/- 0.18, P < 0.001), a higher CFI (0.33 +/- 0.08 vs. 0.13 +/- 0.07, P < 0.001), and a higher binary restenosis rate (54.2% vs. 19.4, P = 0.003). CFI*100 was an independent predictor of restenosis after 9 months (odds ratio 1.07, 95% CI 1.02-1.12, P = 0.016). CONCLUSION: Recruitable collateral blood flow measured during balloon inflation predicts angiographic instent restenosis in PCI patients treated with bare metal stents.     

Magnetic resonance imaging versus Doppler guide wire in the assessment of coronary flow reserve in patients with coronary artery disease

BACKGROUND: Coronary flow velocity reserve (CFVR), defined as the ratio of maximal hyperaemic to baseline flow velocity, has been validated as a marker of physiological significance of a coronary lesion. Clinically, this parameter is measured invasively during X-ray angiography using the Doppler guide wire. With magnetic resonance (MR) imaging it is possible to quantify CFVR non-invasively. DESIGN: The purpose of the study was to compare CFVR, acquired with MR imaging and the Doppler guide wire in patients with coronary artery disease. METHODS: Twenty-two patients suffering from one- or two-vessel coronary artery disease as derived from diagnostic X-ray coronary angiography were included. Coronary flow velocity reserve was measured at baseline and during maximal hyperaemia, obtained by intravenous administration of adenosine using MR phase contrast velocity quantification. Within 2 weeks CFVR was measured invasively with a Doppler guide wire. RESULTS: In 26 coronary arteries CFVR was acquired with both techniques. Mean CFVR in the stenosed and healthy reference arteries was 1.5 +/- 0.7 and 2.7 +/- 1.0 (P < 0.01) respectively for MR measurements and 1.9 +/- 0.7 and 3.1 +/- 0.6 (P < 0.01) respectively for Doppler measurements. Bland-Altman analysis revealed a non-significant mean difference between the two techniques of 0.4 +/- 1.2. CONCLUSION: In a selected group of stable patients with coronary artery disease MR flow velocity quantification provides non-invasive data equivalent to the invasive Doppler guide wire data. Variability in both the MR and Doppler ultrasound measurement resulted in a significant scatter of data without systematic difference.     

Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire.

OBJECTIVES: We tested the hypothesis that coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD) as assessed by a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) is in agreement with CFR measurements assessed by intracoronary Doppler flow wire. BACKGROUND: Contrast-enhanced transthoracic second harmonic echo Doppler is a novel noninvasive method to detect blood flow velocity and reserve in the LAD. However, it has not yet been validated versus a gold-standard method. METHODS: Twenty-five patients undergoing CFR assessment in the LAD by Doppler flow wire were also evaluated by contrast-enhanced transthoracic Doppler to record blood flow in the distal LAD at rest and during hyperemia obtained by adenosine i.v. infusion. In five patients CFR was evaluated twice (before and after angioplasty). RESULTS: As a result of the combined use of i.v. contrast and second harmonic Doppler technology, feasibility in assessing coronary flow reserve equaled 100%. The agreement between the two methods was high. In fact, in all but five patients the maximum difference between the two CFR measurements was 0.38. Overall, the prediction (95%) interval of individual differences was -0.69 to +0.72. Reproducibility of CFR measurements was also high. The limits of the agreement (95%) between the two measurements were -0.32 to +0.32. CONCLUSIONS: Coronary flow reserve in the LAD as assessed by contrast-enhanced transthoracic echo Doppler along with harmonic mode concurs very closely with Doppler flow wire CFR measurements. This new noninvasive method allows feasible, reliable and reproducible assessment of CFR in the LAD.     

Prevalence of microvascular disease in patients with significant coronary artery disease

Coronary flow velocity reserve (CFVR) measurement using intracoronary Doppler techniques has been increasing accepted for the assessment of physiological significance of epicardial stenosis and the functional changes after coronary interventions. However, large discrepancy exists concerning the acute changes of CFVR immediately after intervention. The purpose of this study was to investigate the prevalence of microvascular dysfunction in patients with significant coronary artery disease. Intracoronary Doppler flow measurements were performed in a total of 212 patients who underwent coronary interventions because of significant epicardial stenosis using 0.014" Doppler flow wire (Cardiometrics, Inc, Mountain View, CA). Intracoronary bolus injection of adenosine (12 micrograms for the right coronary and 18 micrograms for the left coronary arteries) was used to induce hyperemic reaction. CFVR was registered as the ratio of average peak velocity during hyperemia (hAPV) to at baseline (bAPV). Successful coronary interventions either by percutaneous transluminal coronary balloon angioplasty (PTCA) or by stenting could significantly improve the CFVR. In 80 patients with PTCA, the bAPV elevated from 16.6 +/- 2.1 cm/s to 20.6 +/- 13.4 cm/s and hAPV from 30.1 +/- 15.9 cm/s to 45.2 +/- 17.7 cm/s (both p < 0.001) with PTCA and the CFVR increased from 1.94 +/- 0.78 to 2.58 +/- 0.87 correspondingly (p < 0.001). Significant elevation of coronary flow parameters were also found in 132 patients with subsequent stent implantation (bAPV from 15.3 +/- 6.7 cm/s to 18.7 +/- 9.1 cm/s, hAPV from 28.7 +/- 14.4 cm/s to 44.3 +/- 17.7 cm/s and CFVR from 1.90 +/- 0.70 to 2.59 +/- 0.87, all p < 0.001). Reduction of CFVR (< 3.0) after intervention still existed in 46 (61.3%) of 80 patients after PTCA and 88 (66.7%) of 132 patients after stenting. Moreover, CFVR < 3.0 were found in 50 (45.9%) of 109 reference vessels in patients with single vessel disease. Significant improvement of coronary flow velocity and coronary flow velocity reserve could be obtained after successful angioplasty. However, microvascualr dysfunction existed in a large proportion of patients either in normal reference vessels or in target vessels after interventions.     

Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?

OBJECTIVES: The purpose of this study in patients with quantitatively determined, poorly developed coronary collaterals was to assess the contribution of ischemic as well as adenosine-induced preconditioning and of collateral recruitment to the development of tolerance against repetitive myocardial ischemia. BACKGROUND: The development of myocardial tolerance to repeated ischemia is nowadays interpreted to be due to biochemical adaptation (i.e., ischemic preconditioning). METHODS: In 30 patients undergoing percutaneous transluminal coronary angioplasty, myocardial adaptation to ischemia was measured using intracoronary (i.c.) electrocardiographic (ECG) ST segment elevation changes obtained from a 0.014-in. (0.036 cm) pressure guidewire positioned distal to the stenosis during three subsequent 2-min balloon occlusions. Simultaneously, an i.c. pressure-derived collateral flow index (CFI, no unit) was determined as the ratio between distal occlusive minus central venous pressure divided by the mean aortic minus central venous pressure. The study patients were divided into two groups according to the pretreatment with i.c. adenosine (2.4 mg/min for 10 min starting 20 min before the first occlusion, n = 15) or with normal saline (control group, n = 15). RESULTS: Collateral flow index at the first occlusion was not different between the groups (0.15 +/- 0.10 in the adenosine group and 0.13 +/- 0.11 in the control group, p = NS), and it increased significantly and similarly to 0.20 +/- 0.14 and to 0.19 +/- 0.10, respectively (p < 0.01) during the third occlusion. The i.c. ECG ST elevation (normalized for the QRS amplitude) was not different between the two groups at the first occlusion (0.25 +/- 0.13 in the adenosine group, 0.25 +/- 0.19 in the control group). It decreased significantly during subsequent coronary occlusions to 0.20 +/- 0.15 and to 0.17 +/- 0.13, respectively. There was a correlation between the change in CFI (first to third occlusion; deltaCFI) and the respective ST elevation shift (deltaST): deltaST = -0.02 to 0.78 x deltaCFI; r = 0.54, p = 0.02. CONCLUSIONS: Even in patients with few coronary collaterals, the myocardial adaptation to repetitive ischemia is closely related to collateral recruitment. Pharmacologic preconditioning using a treatment with i.c. adenosine before angioplasty does not occur. The variable responses of ECG signs of ischemic adaptation to collateral channel opening suggest that ischemic preconditioning is a relevant factor in the development of ischemic tolerance.     

A simplified method to measure coronary blood flow velocity in patients: validation and application of a Judkins-style Doppler-tipped angiographic catheter

To facilitate more rapid and safe measurement of coronary flow velocity reserve in patients, we developed a Judkins-style angiographic catheter tipped with a 20 MHz Doppler crystal. In 19 patients without coronary artery disease, resting and hyperemic (10 mg intracoronary papaverine) mean and phasic coronary flow velocity signals were measured with the Judkins-style and 2.5F intracoronary Doppler catheters at identical coronary loci. Mean coronary flow velocity at rest was similar (14 +/- 8, 10 +/- 7 cm/sec, p = ns), but was higher during hyperemia for the Judkins-Doppler (41 +/- 8 versus 32 +/- 14 cm/sec, p less than 0.05). Coronary flow velocity reserve, calculated as the ratio of mean velocity at rest to mean velocity following papaverine, was 3.3 +/- 1.4 and 3.7 +/- 1.2 units (p = ns) for the Judkins and intracoronary Doppler techniques, respectively (r = 0.801, p less than 0.001). The Judkins-style Doppler catheter technique permits flow velocity and coronary flow velocity reserve measurements that correlate strongly with those of the intracoronary catheter technique, facilitating safe, quick, and accurate assessment of coronary physiology.     

Coronary flow reserve assessment by transthoracic color Doppler echocardiography after primary angioplasty: relationship with recovery of left ventricular function]

BACKGROUND: The aim of this study was to determine the relationship between coronary flow reserve measurement by transthoracic Doppler echocardiography in recent acute myocardial infarction treated with primary coronary angioplasty (PTCA) and recovery of left ventricular function. METHODS: Forty-one consecutive patients (3 patients excluded for not good quality of the Doppler signal) have been studied with: (1) recent first acute myocardial infarction treated with primary PTCA within 6 hours of pain onset; (2) optimal angioplasty result with stent deployment, anti-IIb/IIIa infusion and TIMI 3 flow; (3) lack of type 1 diabetes and/or hypertension; (4) good tolerance to adenosine. Transthoracic Doppler echocardiography was used to record coronary flow velocities in the distal left anterior descending and posterior descending coronary arteries at rest and after infusion of adenosine. Coronary flow reserve was measured after 11 +/- 1 days from the acute event. The wall motion score index (WMSI) was calculated at baseline, 1 month and 3 months from myocardial infarction. RESULTS: Patients of group A (n = 29 with coronary flow reserve > or = 1.6) showed a progressive and significant recovery of left ventricular function at follow-up. Patients of group B (n = 9 with coronary flow reserve < 1.6) had persistent left ventricular dysfunction at 3 months (ANOVA, p < 0.0001). WMSI was 1.64 +/- 0.26 in group A and 1.81 +/- 0.16 in group B (p = 0.09) at baseline; 1.30 +/- 0.26 in group A and 1.75 +/- 0.16 in group B (p < 0.0001) at 1 month; and 1.20 +/- 0.25 in group A and 1.73 +/- 0.17 in group B at 3 months. There was an inverse correlation between coronary flow reserve and WMSI at 1 month (r = -0.564, p < 0.0001), and at 3 months (r = -0.583, p < 0.0001). On multivariate analysis baseline WMSI and coronary flow reserve were the only predictors of 1-month WMSI recovery and of WMSI recovery at 3 months. CONCLUSIONS: Coronary flow reserve by transthoracic color Doppler echocardiography is a useful method for predicting left ventricular function recovery in patients after primary PTCA.     

Regional myocardial perfusion reserve determined using myocardial perfusion magnetic resonance imaging showed a direct correlation with coronary flow velocity reserve by Doppler flow wire

Aims: Quantitative analysis of rest–stress myocardial perfusionmagnetic resonance imaging (MRI) can provide assessments ofregional myocardial perfusion reserve (MPR). The purpose ofthis study was to compare regional MPR determined by myocardialperfusion MRI with coronary flow reserve (CFR) by intracoronaryDoppler flow wire. Methods and results: Twenty patients with suspected coronary artery disease (CAD)were studied. Average peak velocity was measured by Dopplerflow wire in the resting state and during adenosine triphosphate(ATP) stress in 36 coronary arteries. CFR measurements for eachpatient were performed in the culprit and one non-culprit non-stenoticartery. First-pass, contrast-enhanced myocardial perfusion MRimages were obtained in the resting state and during ATP stresswithin the week before the Doppler wire procedure. Regionalmyocardial blood flow (MBF) was quantified in 16 myocardialsegments by analysing arterial input and myocardial output usinga Patlak plot method. MPR was calculated as stress MBF dividedby rest MBF. CFR measured by Doppler flow wire was comparedwith MPR in the myocardial segments corresponding to vesselterritories. The average MPR measured by perfusion MRI was 1.77± 0.62 for the culprit arteries and 3.45 ± 0.78for the non-culprit arteries, respectively (P < 0.001). Theaveraged CFR by Doppler flow wire was 1.72 ± 0.44 inthe culprit arteries and 3.14 ± 0.74 in the non-culpritarteries, respectively (P < 0.001). For both culprit andnon-culprit vessel groups, significant direct correlations wereobserved between MR assessments of MPR and Doppler assessmentsof CFR (culprit artery: R = 0.87, Non-culprit artery: R = 0.86)On Bland–Altman analysis, the mean differences betweenMPR determined by myocardial perfusion MRI and CFR measuredby Doppler wire were 0.05 in culprit arteries (95% limit ofagreement; –0.65 to 0.56) and 0.36 in non-culprit arteries(95% limit of agreement; –1.24 to 0.44). The sensitivityand specificity of MR measurement of MPR for predicting physiologicallysignificant reduction of Doppler CFR (<2) was 88% (95% CI61.7–98.5) and 90% (95% CI 68.3–98.8), respectively. Conclusion: The current results using Doppler flow wire as a reference methoddemonstrated that quantitative analysis of stress–restmyocardial perfusion MRI can provide a non-invasive assessmentof reduced MPR in patients with CAD.     

Effect of acute atrial fibrillation on phasic coronary blood flow pattern and flow reserve in humans.

AIMS: To assess the effect of experimentally induced atrial fibrillation on coronary flow in humans. METHODS AND RESULTS: In 16 patients (10 men, mean age 43+/-13 years) with normal coronary vessels, baseline and hyperaemic blood pressure and Doppler phasic coronary flow velocity were measured, using a 0.014 inch intracoronary Doppler flow wire, during sinus rhythm, experimentally induced atrial fibrillation, and right atrial pacing at a similar heart rate to that during atrial fibrillation. Coronary flow velocity integral per minute increased significantly during both right atrial pacing and atrial fibrillation compared to sinus rhythm, but during right atrial pacing the increase was greater (85+/-43% vs 52+/-25%, P<0.001). This difference persisted even after correction for the product of heart rate and blood pressure (1.15+/-0.51 vs 0.97+/-0.46, respectively, P<0.02). In a further 12 paced patients (seven men, mean age 54+/-10 years) with complete atrioventricular block the induction of atrial fibrillation (atrial fibrillation with regular RR interval) caused no significant changes in coronary flow velocity variables. CONCLUSIONS: Acute atrial fibrillation in humans causes an increase in coronary flow that is, however, insufficient to compensate for the augmented myocardial oxygen demand, mainly because of the irregularity in the ventricular rhythm that exists during atrial fibrillation.