Validation of noninvasive assessment of coronary flow velocity reserve in the right coronary artery

A comparison of transthoracic echocardiographic results with intracoronary Doppler flow wire measurements

Harald Lethena,*, Hans P. Triesa, Stefan Kerstinga and Heinz Lambertza

a Department of Cardiology, Deutsche Klinik für Diagnostik, Aukammallee 33, D-65191 Wiesbaden, Germany

* Corresponding author: Tel.: +49-611-577663; fax: +49-611-577325
E-mail address: lethen.kardio{at}dkd-wiesbaden.de

Received 6 March 2003; revised 4 April 2003; accepted 23 April 2003


    Abstract
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 
Aims Assessment of coronary flow velocity reserve (CFR) noninvasively using transthoracic Doppler echocardiography (TDE) is validated for the left anterior descending artery only. We evaluated the feasibility and reproducibility to assess CFR using TDE in the right coronary artery, and compared the results with intracoronary Doppler flow wire (DFW) measurements.

Methods and results Introduction of a modified apical 2-chamber view allows visualization of the posterior descending branch of the right coronary artery (RPD). 42 consecutive patients (31 men, mean age 61±10) with suspected coronary artery disease scheduled for coronary angiography underwent CFR assessment using TDE in fundamental imaging mode; the results were compared with DFW measurements. CFR could be taken noninvasively in 81% (34/42); in case of right dominant- or balanced coronary circulation type success rate was significantly higher (87%; 33/38) than in case of left dominant coronary circulation (25%; 1/4). Correlation between echocardiographically and intracoronary derived CFR results was significant (r=0.85, P<0.0001), as well as reproducibility (r=0.94, P<0.0001) and interobserver variability (r=0.78, P<0.0001).

Conclusion Coronary flow reserve assessed in the peripheral RCA by TDE concurs very closely with intracoronary Doppler flow wire CFR results. This new approach allows feasible, accurate and reproducible measurement of CFR in the RCA.

Key Words: Coronary flow reserve • Echocardiography • Right coronary artery


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 
The assessment of coronary flow velocity reserve (CFR) has proven to be useful in the detection of relevant coronary artery disease as well as microvascular circulatory disorder. Current data suggest that intracoronary measurement of CFR adds valuable information to angiographic results with important clinical implications.1–5Transthoracic Doppler echocardiography (TDE) has been introduced as a new diagnostic approach to visualize coronary blood flow and measure CFR non-invasively, but clinical application is limited as this technique is validated for the left anterior descending artery only.6–10

Recently, a technique to image the posterior descending branch of the right coronary artery (RPD) was described.11As there is considerable patient-to-patient variability regarding the size and distribution of the coronary branches with the territory of the RPD not always being supplied by the right coronary artery,12it was the purpose of this investigation to: (1) evaluate the success rate of this new approach for imaging blood flow and assessing CFR in the RPD, (2) examine the reproducibility and interobserver variability, and (3) comparethe noninvasive results with invasive CFR measurements using intracoronary Doppler flow wire (DFW).


    2. Methods
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 
2.1. Patients
Forty-two consecutive patients (31 men, 38 to 85 years, mean age 61±10; mean BMI 27±3.5kg/m2) with suspected coronary artery disease scheduled for diagnostic coronary angiography were prospectively studied. Patients with atrial fibrillation or previous posterior myocardial infarction were excluded from the study. Cardiac medication except aspirin, ticlopidine, clopidogrel, or short acting nitrates and intake of xanthin-containing food or beverages like chocolate, tea, coffee or coke was stopped at least 24h before CFR was taken. Noninvasive assessment of CFR in the RPD was performed within 24h before coronary angiography by one experienced echocardiographer blinded to any patient data. Intracoronary DFW CFR measurement was done in the RPD during the angiographic examination. All patients were informed regarding the purpose of the study and gave informed consent.

2.2. Echocardiographic examination
Transthoracic echocardiographic examination was performed with an electronic phase array ultrasound system (Sequoia C256®, Siemens-Acuson, Mountain View, CA, USA). Patients were examined in stable 90° left lateral recumbent position. A broadband transducer (3V2c) was used. Colour-coded Doppler was performed in fundamental imaging mode at 2.5MHz with a Nyquist limit being at 12–16cm/sec., whereas 2.0MHz was used for pulsed-wave Doppler studies with minimal angle correction. Stop frames and clips were digitally recorded and stored on magneto-optical disks. All measurements were done off-line using an ultrasound-machine incorporated analysis and calculation package.

2.3. Visualization of coronary flow in the RPD
A systematic approach was made to visualize the RPD in the posterior interventricular groove (Fig. 1). First, the left ventricle was imaged in a standard apical two-chamber view. From this position the transducer was slightly rotated anticlockwise and carefully tilted anteriorly, until coronary blood flow in the basal part of the posterior interventricular groove was identified by colour Doppler (Fig. 2).



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Fig. 1 Diaphragmatic aspect of the heart showing the posterolateral branch (RPL) and in the posterior interventricular sulcus the posterior interventricular descending branch (RPD) of the right coronary artery (RCA). CS=coronary sinus

 


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Fig. 2 Upper panel: Coronary angiography of the right coronary artery in 30°/20° RAO projection. The Doppler flow wire is positioned in posterior interventricular descending branch (RPD, arrows) of the right coronary artery. Middle panel: Color Doppler showing the proximal part of the posterior interventricular descending branch (RPD, arrow) in the posterior interventricular groove; a modified apical 2-chamber view is used. LV=left ventricle, MV=mitral valva, LA=left atrium. Lower panel: Characteristic biphasic spectral Doppler and Doppler flow wire traces of coronary flow velocity at rest and during hyperemia to measure coronary flow reserve (CFR) in the distal right coronary artery in the same patient. Noninvasive CFR is 2.4, invasive 2.4 is measured.

 
2.4. Echocardiographic assessment of CFR
After detection of the characteristic predominant diastolic biphasic blood flow, the sample volume (gate size 2.0–3.5mm) was positioned for spectral Doppler analysis of coronary blood flow. Flow velocity recordings were performed in a stable transducer position at rest and during maximal hyperemia, which was induced by intravenous administration of adenosine (140µg/kg/min). Systolic-diastolic average peak velocities at rest and during maximal hyperemia (mean peak velocity) were used for off-line analysis of spectral Doppler tracings to calculate CFR (Fig. 2). The values of three consecutive beats were averaged to calculate the flow velocity at rest and during hyperaemia. Additionally, CFR was calculated by the relation of diastolic peak velocity during hyperaemia to diastolic peak velocity at rest (maximal peak velocity).

2.5. Reproducibility and interobserver variability
To assess reproducibility of TDE CFR measurements, coronary flow recordings were performed twice on the same day in a subgroup of 14 patients by one echocardiographer; interobserver variability was assessed by analysing off line CFR measurements of 24 patients by two observers blinded to any patient data. Both, mean peak velocity and maximal peak velocity were calculated.

2.6. Coronary angiography
Coronary angiography following a standard procedure was performed in every patient. The coronary distribution type was evaluated: Patients with the right coronary artery giving rise to the RPD had either a ‘right-dominant’ or ‘balanced’ coronary circulation; in case of a ‘left-dominant’ circulation the territory of the RPD was supplied by the terminal portion of the circumflex coronary artery.12

2.7. Intracoronary measurement of CFR using Doppler flow wire
CFR was measured immediately after diagnostic coronary angiography, using intracoronary Doppler flow wire. FloMap 5500®(Cardiometrics Inc., Rancho Cordova, CA, USA) and Doppler-tipped flow wire (0.014-in, 12MHz, FloWire®, Cardiometrics Inc.) were used. The tip of the flow wire was carefully positioned in a non-tortuous segment of the distal RPD (Fig. 2). Intravascular velocity measurement in the RPD was achieved at rest and during maximal vasodilatation (adenosine, 140µg/kg/min). CFR was calculated by the ratio of mean maximal systolic-diastolic velocity at hyperemia to the corresponding velocity at rest, using a machine incorporated software system (Fig. 2). All examinations were recorded on S-VHS-videotape.

2.8. Duration of TDE- and DFW-CFR measurement
In a subgroup of 15 patients (TDE CFR) respectively 18 patients (DFW CFR) the examination time needed to measure CFR, beginning either with introduction of the DFW into the femoral artery or with imaging of the apical 2-chamber view, was recorded.

2.9. Statistical analysis
Continuous variables are expressed as mean±standard deviation (SD). The comparison of CFR assessed by the two methods and the analysis of reproducibility and interobserver variability was evaluated according to the method of Bland and Altman (plot of difference against mean)13and by use of a linear regression analysis expressed as the slope and the correlation coefficient (r). 95% confidence intervals were calculated. Statistical significance was considered at P<0.05. All calculations were performed with MicrosoftTMExcel 2000 statistical analysis features (Microsoft Corporation, Redmond, WA, USA).


    3. Results
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 
TDE assessment of CFR in the RPD was feasible in 34/42 patients (81%). Patient characteristics, the coronary perfusion type as well as results of echocardiographic and invasive CFR studies are summarized in Table 1.


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Table 1 Coronary flow velocity reserve data of 34/42 patients with successful non-invasive (TDE) CFR assessment

 
3.1. Adenosine
Adenosine was well tolerated in all patients; no relevant hemodynamic side effects, conduction disturbances or clinical symptoms like headache, flushing or pectanginal pain were seen. Mild to moderate palpitations occurred in 10/34 patients (29%).

3.2. Coronary angiography
In no patient the right coronary artery was occluded. In 38/42 patients (90%) the territory of the RPD was supplied by the right coronary artery, in 4/42 patients a left dominant circulation was found.

3.3. TDE measurement of CFR in the RPD
Adequate pulse-wave Doppler signals to measure CFR noninvasively in the RPD were obtained in 81% (34/42) of patients. In case of a right dominant- or balanced type of coronary circulation CFR was taken successfully in 87% (33/38), in case of a left dominant coronary circulation with the circumflex coronary artery supplying the territory of the RPD coronary flow was detected in 25% (1/4) only (Table 1).

3.4. Comparison of TDE (mean peak velocity) and invasive measurement of CFR
In all 34 patients in whom CFR could be assessed noninvasively by TDE (mean peak velocity) CFR was measured invasively using DFW. Mean TDE CFR was 2.54 (SD±0.56), mean DFW CFR 2.66 (SD±0.71) (Table 1). The correlation between TDE CFR and DFW CFR was significant (r=0.85, P<0.0001), the mean difference of CFR data was 0.29±0.09 (SD±0.26, 95%-confidence interval) showing high agreement (Fig. 3a,b).



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Fig. 3 Plot of linear regression analysis (a) and mean difference (b) comparing CFR measured by TDE (mean peak velocity) and DFW methods. CFR=coronary flow velocity reserve, DFW=intracoronary Doppler flow wire, TDE (mean peak velocity)=transthoracic Doppler echocardiographic CFR calculated from systolic-diastolic average peak flow velocity, RPD=posterior descending branch of the right coronary artery, {Delta}=difference.

 
3.5. Comparison of TDE (max peak velocity) and invasive measurement of CFR
TDE CFR results calculated from the maximal diastolic flow velocity correlated well with intracoronary DFW measurements. Maximal TDE CFR was slightly higher (2.72 [SD±0.68]) than mean DFW CFR (2.66 [SD±0.71]) (Table 1). The correlation coefficient (r=0.84, P<0.0001), the mean difference of CFR data (0.29±0.09) as well as the limits of agreement and the level of significance (SD±0.26, 95%-confidence interval) revealed good agreement of both methods (Fig. 4a,b).



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Fig. 4 Plot of linear regression analysis (a) and mean difference (b) comparing CFR measured by TDE (max peak velocity) and DFW methods. TDE (max peak velocity)=transthoracic Doppler echocardiographic CFR calculated from maximal diastolic flow velocity. Other abbreviations as in Fig. 3.

 
3.6. Reproducibility of TDE CFR
CFR was assessed noninvasively twice on the same day by one echocardiographer. Correlation was high (r=0.94, P<0.0001) and the mean difference small enough (0.16±0.08, SD±0.15, 95%-confidence interval) to indicate good reproducibility for echocardiographically derived CFR results (Fig. 5a,b).



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Fig. 5 Plot of linear regression analysis (a) and mean difference (b) showing the relation between the 1st and 2nd TDE CFR measurement performed on the same day by the same examiner. 1st assessm=first assessment, 2nd=second. Other abbreviations as in Fig. 3.

 
3.7. Interobserver variability
Interobserver variability of TDE CFR between two blinded observers showed good agreement when comparing mean peak velocity data (r=0.78, P<0.0001, mean difference=0.30±0.12, SD±0.32, 95%-confidence interval) and even better results when maximal peak velocity data were analysed (r=0.89, P<0.0001, mean difference=0.27±0.11, SD±0.23, 95%-confidence interval) (Fig. 6a,b; Fig. 7a,b).



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Fig. 6 Plot of linear regression analysis (a) and mean difference (b) comparing TDE CFR calculated by two blinded observers for analysis of interobserver variability. Abbreviations as in Fig. 3.

 


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Fig. 7 Plot of linear regression analysis (a) and mean difference (b) comparing TDE (max peak velocity) CFR calculated by two blinded observers for analysis of interobserver variability. Abbreviations as in Fig. 3and Fig. 4.

 
3.8. Requirements
Average duration of TDE CFR assessment in the RPD was slightly more time consuming (14.7min [SD±3.9min], n=15) compared with intracoronary DFW measurement (10.6min [SD±2.6 min], n=18). The average radiation time required to position the DFW in the RPD was 2.6min (SD±1.7min), radiation exposure caused a mean doses of 465cGy*cm2(SD±241cGy*cm2).


    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 
In this study the technique to assess coronary flow reserve in the posterior descending brench of the right coronary artery is described. Noninvasively taken CFR results are compared with invasive CFR measurements using Doppler-tipped flow wire. The main findings are: (1) TDE measurement of CFR is feasible in the majority of patients, with (2) reproducible results and low interobserver variability, and (3) high agreement of noninvasive and invasive CFR results.

4.1. Methodologic considerations of CFR measurement in the right coronary artery
To visualize coronary flow and measure CFR in the RPD of the RCA a modified apical two-chamber view of the left ventricle is used in this study (11). According to the anatomical situation this technique differs from the method described to take LAD flow and some potential difficulties have to be considered. CFR in the LAD can be assessed by using high frequency transducers (7–12MHz) because of the proximity of this vessel to the chest wall.7,9,14,15However, this technique is not suitable for imaging peripheral RCA flow because of the greater distance between the transducer and the basal inferior cardiac wall. Therefore, a lower imaging frequency (2.5–3.5MHz) is required to overcome the problem of inadequate penetration depth of high frequency echocardiography.

The coronary anatomy shows considerable patient-to-patient variability. In more than 90% of patients the coronary circulation type is ‘right-dominant’ or ‘balanced’, meaning that the territory of the RPD is supplied by the right coronary artery. In about 8% the coronary circulation is ‘left dominant’ with the left circumflex artery mainly supplying the territories of the posterior descending and the posterolateral left ventricular branch.12In these cases the diameter of the RPD of the right coronary artery might be too small to acquire an accurate Doppler flow profile. Furthermore, recording an accurate systolic-diastolic pulsed-wave Doppler signal is often hampered by respiration and lateral and vertical motion of the inferior cardiac wall during the cardiac cycle. Assessment of Doppler flow velocity signals in apnea can only partially resolve this problem.

On the other hand, the approach for the assessment of CFR in the RCA shows some advantages compared with the technique used for the LAD. The modified apical two-chamber view allows alignment of the ultrasound beam roughly parallel to the course of the RPD providing an adequate registration of coronary flow velocity. Furthermore, the coronary sinus is a helpful anatomical landmark to identify the location of the RPD; the absence of bigger side branches of the RCA in this area and the straight course of the vessel towards the apex allow a well reproducible transthoracic echocardiographicexamination.

4.2. Transthoracic echocardiographic assessment of mean peak- or maximal peak velocity to take CFR
For off-line analysis of spectral Doppler tracings, both systolic-diastolic average peak velocities (mean peak velocity) and diastolic peak velocities (maximal peak velocity) were used in all patients to calculate CFR. This was done because recording of an accurate systolic-diastolic pulsed-wave Doppler signal may be difficult in some patients due to the lateral and vertical motion of the inferior cardiac wall during the cardiac cycle. Maximal peak velocity TDE CFR was slightly higher than Doppler flow wire derived results, whereas CFR values calculated from mean peak velocity data were slightly lower. However, the comparison of both measurements with invasive measurements showed almost identicalresults for the correlation coefficient and the mean difference of CFR data. Therefore, in concordance to the results found for TDE CFR assessment in the LAD,7both values can be used for calculation of CFR in the RPD of the RCA.

4.3. Agreement of TDE and Doppler flow wire measurements
Invasive measurement of coronary flow velocity is a validated and established method for assessment of CFR, providing useful clinical and physiologic information. However, the main disadvantage of this technique is its invasiveness at relatively high costs. TDE for CFR measurement is non-invasive, clinically widely accessible and inexpensive, when compared with CFR assessment performed in the catheterization laboratory, but clinical use of this technique so far was limited to the LAD. In this study, a close agreement between CFR determined in the RPD of the RCA by TDE and intracoronary Doppler flow wire measurements was found. This significant correlation of both methods could be demonstrated for systolic-diastolic average peak velocity data (mean peak velocity) as well as for diastolic peak velocity data (maximal peak velocity). This suggests that CFR in the RPD of the right coronary artery can be assessed reliably in the echocardiographic laboratory.

4.4. Relevance of the coronary anatomy
The coronary anatomy shows considerable patient-to-patient variability. In this study 90% of patients had a ‘right-dominant’ or ‘balanced’ type of coronary circulation; in all of these patients angiographically a RPD running in the posterior interventricular groove was detected and the success rate to measure CFR was high (87%) in these patients. In 10% of patients a ‘left dominant’ coronary distribution type was found and only one of these patients showed angiographically a RPD originating from the right coronary artery. In this patient TDE CFR measurement could be performed; in the other patients with a ‘left dominant’ type of coronary circulation the RPD of the right coronary artery was to small or missing, which prevented detection of the RCAechocardiographically.

4.5. CFR measurement reproducibility and interobserver variability
Visualizing the RPD using color Doppler flow allows appropriate positioning of the PW Doppler sample volume; with regard to the learning curve for the detection of the RPD flow signal, the overall success rate for CFR assessment in this study was 81%. Measuring CFR twice the same day in a subgroup of patients showed excellent short term reproducibility of the method (mean difference: 0.16), paralleling the reproducibility of intracoronary DFW16and TDE CFR measurement in the left anterior descending artery.9,17In addition to the precision of the measurements, the noninvasiveness of this approach aids in keeping measurements repeatable.

The interobserver variability was good when systolic-diastolic average peak velocity data (mean peak velocity) were analyzed (mean difference: 0.32), and slightly higher for diastolic peak velocity data (maximal peak velocity, mean difference: 0.27). This mild difference is not unexpected because recording an accurate systolic-diastolic pulsed-wave Doppler signal can be limited by respiration and lateral and vertical motion of the inferior cardiac wall during the cardiac cycle.


    5. Study limitations
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 
Some methodologic and hemodynamic factors may have affected the comparison of both methods: (1) Due to technical reasons, DFW and TDE assessment of CFR were not performed simultaneously. (2) Coronary flow velocities measured with TDE may be slightly different when compared with the values assessed by DFW technology; however, the difference in absolute velocities does not affect the assessment of CFR if the pulsed wave Doppler angle remains constant during the measurement at rest and hyperemia. (3) It is not possible to position the tip of the DFW exactly at the same place as the sample volume during TDE. However, in all patients the tip of the DFW was carefully positioned in a peripheral, non tortuous segment of the RPD to obtain a signal of high quality. (4) In this study patients with suspected coronary artery disease and different underlying cardiac diseases were investigated. However, it was not the purpose of the study to evaluate the characteristics of CFR in various cardiac disorders, but to investigate the reliability and reproducibility of TDE CFR.

5.1. Clinical implication
TDE for noninvasive assessment of CFR provides useful quantitative information regarding the functional status of coronary arteries. In combination with coronary morphologic findings obtained from cardiac catheterization, CFR has relevant clinical implications for patients scheduled for invasive evaluation and treatment of coronary artery disease. So far echocardiographic assessment of CFR was validated for the left anterior descending artery only. This study shows, that TDE CFR assessment in the RPD of the right coronary artery closely agrees with intracoronary DFW measurement. This new noninvasive approach allows feasible, accurate and reproducible measurement of CFR in the RCA with results paralleling those found for transthoracic echocardiographic evaluation of CFR in the LAD. Therefore this new method has the potential to expand noninvasive assessment of CFR.


    References
 Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Study limitations
 References
 

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