Skip Navigation

European Journal of Echocardiography 2006 7(2):134-140; doi:10.1016/j.euje.2005.04.015
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ahmari, S. A.L.
Right arrow Articles by Chandrasekaran, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ahmari, S. A.L.
Right arrow Articles by Chandrasekaran, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2005, The European Society of Cardiology

Doppler derived coronary flow reserve during dobutamine stress echocardiography further improves detection of myocardial ischemia*

Saeed A.L. Ahmaria,b,1, Karen Modestoa, Jared Buncha, Vicky Stussya, Amy Dichaka, James Sewarda, Patricia Pellikkaa and Krishnaswamy Chandrasekarana,*

aEchocardiography Lab, Cardiology division, Mayo Clinic, 200 First Street SW, Gonda 6-138 NW, Rochester, MN 55905, USA
bPrince Sultan Cardiac Center, P.O. Box 340301, Riyadh 11333, Saudi Arabia naman45{at}hotmail.com

Received 4 December 2004; received in revised form 18 April 2005; accepted after revision 23 April 2005.

* Corresponding author. Tel.: +1 507 284 3581; fax: +1 507 284 1732. k.chandra{at}mayo.edu


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 Limitation of the study
 Clinical implication of this...
 Conclusion
 Notes
 References
 
Background The coronary flow velocity (CFV) has been used to estimate coronary flow reserve (CFR) during dobutamine stress echocardiography (DSE). However, the relationship of the CFR to myocardial wall thickening (WT) has not been investigated.

Objectives The aims of this study were: (1) to assess the feasibility of obtaining systolic and diastolic CFV and thus CFR during DSE and (2) to assess the relation between CFR and stress induced WT.

Methods Distal left anterior descending CFV was recorded by transthoracic Doppler echocardiography during DSE. Systolic and diastolic velocities were measured at rest, low and peak dobutamine doses, simultaneously, WT of distal anteroseptal segment was assessed by 2D-guided M-mode. The CFV and CFR of patients with normal WT defined as thickening of >50% (group 1) at peak stress were compared to that of patients with abnormal WT (group 2).

Results A total of 67 patients, 34 females and 33 males (mean age of 66.5±14.5 years) were studied. The feasibility of assessing the CFR was 97% from peak diastolic velocity, 91% from diastolic time velocity integral, 91% from peak systolic velocity, and 90% from systolic time velocity integral. Contrast agent was used in 6 patients (7%) to obtain the CFV. Twenty-five of 67 patients demonstrated abnormal wall thickening. The percentage of WT was 30.9±15.7% in group 2 compared to 80.8±24.3% in group 1 (p<0.0001). The 25 patients in group 2, who developed abnormal WT, demonstrated significantly lower CFR at low dose, as well as at peak dobutamine dose compared to patients in group 1 (1.55±0.5 vs. 2.03±0.6, p<0.008).

Conclusion CFV and CFR assessments are feasible during DSE with second harmonic imaging in most patients without use of contrast agent. CFR assessment during DSE correlates well with wall thickening and was able to detect ischemia early before development of wall motion abnormality.

Keywords: Coronary flow reserve; Wall thickening

Noninvasive assessment of CFV and CFR has been demonstrated with several imaging techniques including magnetic resonance imaging,1 positron emission tomography,2 transesophageal echocardiography,3 and contrast echocardiography.4 Transthoracic Doppler assessment of CFV and CFR during pharmacological stress tests has been validated by direct comparison to intracoronary Doppler wire measurements.5–8 Although CFR estimated from LAD by transthoracic Doppler echocardiography (TTDE) correlates well with wall motion score index,8 there are no data demonstrating the relationship of CFV and CFR to systolic wall thickening. Therefore, the aims of this study were: (1) to assess the feasibility of obtaining systolic and diastolic CFV and thus CFR of LAD during DSE, and (2) to correlate the CFR to dobutamine stress induced systolic WT.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 Limitation of the study
 Clinical implication of this...
 Conclusion
 Notes
 References
 
We enrolled prospectively consecutive patients older than 18 years referred to stress echo laboratory for clinically indicated DSE. We excluded patients with recent myocardial infarction (within 2 weeks), unstable angina, previous coronary bypass surgery, uncontrolled hypertension, significant valvular heart disease and significant arrhythmia. The Institution Review Board at the Mayo Clinic approved the study and a written consent was obtained from the patients.

Dobutamine stress echocardiography
All patients underwent echocardiography at rest for the assessment of systolic function, regional wall motion abnormality (RWMA), and valve integrity with Color Doppler imaging. A 2D echo guided M-mode scan of the left ventricle (LV) at mid to apical LV was obtained from the lower parasternal short axis view at rest, low dose dobutamine and peak dose dobutamine stress. The wall thickening was measured from the M-mode measurements. DSE was performed with incremental dose of dobutamine from 5mcg/kg/min to 40mcg/kg/min at 3-min intervals. The dobutamine infusion was terminated if the patient achieved 85% of age predicted maximum heart rate or developed any of the following: RWMA of at least moderate severity, significant arrhythmia, severe hypertension (Systolic BP >220mmHg) or hypotension (Systolic BP<80mmHg). The following views were obtained at rest and at each stage of stress: parasternal long and short axis views, apical two and four-chamber views. Atropine (0.25mg–2mg) was administered intravenously if 85% of predicted maximum heart rate is not achieved. Contrast agent (Definity®) was administrated intravenously in a dose of 0.3ml and flushed with 3ml of saline over 30s to improve the endocardial edge detection in difficult studies and to improve detection of the CFV.

Assessment of systolic wall thickening
Percent change in the systolic wall thickening of the anterior septum was calculated from the 2D guided M-mode at rest and at peak dobutamine stress.

Wall thickening of <50% was used to represent ischemia as shown in previously published animal and human studies.9,10 Based on the WT response at peak dobutamine stress, the patients were divided into group 1 – wall thickening >50%, normal response, and group 2 – wall thickening of <50%, abnormal response.

Coronary flow velocity assessment
LAD flow was identified by color flow Doppler using 5MHz transducer with second harmonic imaging, from the lower parasternal window. Imaging plane was adjusted to obtain the long axis view of the vessel to improve the alignment of Doppler interrogation of the LAD flow. Angle correction was used when the angle between the LAD flow and the Doppler beam was >20°. The CFV of distal LAD was obtained at rest, at low dose dobutamine (10mcg/kg/min) and at peak dobutamine stress. Complete description for obtaining the CFV in the LAD bed has been descried earlier.5

Off-line measurements
We used the off-line workstation (Image Vue, Nova Microsonics, Allendale, New Jersey) to analyze the M-mode and coronary flow Doppler tracings. From the M-mode the following measurements were obtained: left ventricle end systolic and end diastolic dimensions (LVESD, LVEDD) in mm, interventricular septum and posterior wall thickness in systole and diastole. The % wall thickening of the anterior septum was obtained at rest, low dose dobutamine and at peak dobutamine stress, and was calculated from the equation (end systolic thickness–end diastolic thickness/end diastolic thickness)100.

From the pulse Doppler interrogation of the LAD flow, the following measurements were obtained: peak systolic velocity (PSV), systolic time velocity integral (STVI), peak diastolic velocity (PDV), and diastolic time velocity integral (DTVI). The CFV measurements were obtained at rest, low dose, and at peak stress. All M-mode and Doppler measurements were averaged from three consecutive sinus beats. The CFR was calculated at low dose dobutamine as the ratio of low dose dobutamine DTVI to baseline DTVI of CFV. Similarly, CFR at peak dobutamine was calculated as the ratio of the DTVI at peak dobutamine to the baseline DTVI of CFV.

Statistics
The continuous variables were expressed as mean±standard deviation and categorical variables as percentiles. Differences between groups 1 and 2 were tested with 2-tailed paired or unpaired t-test as appropriate, Fisher exact and Chi-squared tests were used as needed. A receiver operating characteristic curve was used to define the sensitivity and specificity of calculated CFR from different CFV in detecting abnormal WT. A probability level <0.05 was considered statistically significant.


   Results
Top
 Abstract
 Methods
 Results
Discussion
 Limitation of the study
 Clinical implication of this...
 Conclusion
 Notes
 References
 
Dobutamine stress echocardiography
We studied 67 patients (33 males, and 34 females), mean age of 66.8±13.8 years. The clinical characteristics are summarized in Table 1. All patients tolerated the procedure without complications. The DSE hemodynamics are summarized in Table 1. The mean heart rate increased from 68±11 beats/min to 130.7±15.1 beats/min at peak stress (p<0.0001). Systolic blood pressure increased from 137.4±21.1mmHg to 141.8±28.8mmHg (p=ns) and mean diastolic blood pressure decreased from 75.5±9mmHg to 69.2±10.7mmHg (p<0.0001). Atropine was required in 46 (68%) patients. Contrast agent was required to enhance the endocardial border detection and to enhance CF Doppler signal in6 7% of patients. At peak dobutamine stress, M-mode of the anteroseptal segment demonstrated normal (>50%) wall thickening in 42 patients (group 1), and decreased (<50%) wall thickening in 25 patients (group 2). The mean wall thickening in group 2 was 30.9±15.7% compared to 80.8±24.3% in group 1, Table 4. Among these 25 patients, the anteroseptal RWMA was observed on 2D in only 10 patients.


View this table:
[in this window]
[in a new window]

  		Table 1 Patient clinical characteristics

 
Feasibility of recording coronary flow velocities during dobutamine stress echocardiography
The feasibility of recording the systolic and diastolic CFV in all patients at baseline, low dobutamine dose, and peak dobutamine dose was greater than 90%. Details of the feasibility of measuring different CFV at different stages of stress are shown in Table 2. The changes in the CFV from baseline to low dobutamine dose and to peak dobutamine dose are summarized in Table 3. The feasibility of obtaining the CFR was high from diastolic compared to systolic velocities, PDV, 97%, DTVI, 91% vs. PSV, 91%, and STVI, 90%.


View this table:
[in this window]
[in a new window]

  		Table 2 Feasibility of recording CFV during DSE

 


View this table:
[in this window]
[in a new window]

  		Table 3 CFV measurements obtained during DSE

 
Coronary flow velocity and coronary flow reserve response to wall thickening
The baseline coronary DTVI was higher in group 2 compared to group 1, 17.4±11.2cm vs. 13.3±5.4cm, p<0.05, Fig. 1a. Normal wall thickening (WT) response to dobutamine infusion in group 1 was paralleled with proportional increase in CFV compared to a blunted response in group 2 who also showed abnormal WT response to dobutamine infusion, Fig. 1a. The CFR was significantly lower at low dobutamine dose (10mcg) as well as at peak dobutamine stress (40mcg) in group 2 compared to group 1, Fig. 1b. The CFR calculated from both diastolic and systolic CFV (PDV, DTVI, PSV, and STVI) were lower in group 2 compared to group 1, Table 4. CFR ratio of 1 calculated from DTVI provided a sensitivity of 85% and a specificity of 70% to separate group 2 from group 1. Sensitivity and specificity of calculated CFR from PDV was 72%, and 60%, PSV, 70%, and 50%, STVI, 42%, and 55%.


Figure 1
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 1 (A) Coronary flow velocity (diastolic time velocity integral) response to dobutamine infusion in patients with normal wall thickening, group 1, on the left, and in patients with abnormal wall thickening, group 2, on the right. (B) Attenuated calculated CFR from diastolic time velocity integral in group 2 compared to group 1 patients, at both low and peak dobutamine doses.

 


View this table:
[in this window]
[in a new window]

  		Table 4 Clinical, DSE, and CF data of group 1 and group 2 patients

 
Examples of CFV in a patient with normal WT response to dobutamine stress, and in a patient with abnormal WT response are shown in Figs. 2 and 3Go, respectively.


Figure 2
View larger version (53K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 2 Normal CFR in a patient from group 1. Notice the proportional increase in both systolic and diastolic components of CFV from baseline (A) to peak dobutamine dose (B).

 


Figure 3
View larger version (35K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 3 Abnormal CFR in a patient from group 2 who demonstrated blunted response of both systolic and diastolic CFV from baseline (A) to peak dobutamine dose (B).

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
Limitation of the study
 Clinical implication of this...
 Conclusion
 Notes
 References
 
This study demonstrated that both systolic and diastolic CFV during DSE can be obtained using high frequency transducer and second harmonic imaging, without requiring contrast agents in 90% of the patients. In contrast Takeuchi et al.8 demonstrated a 90% feasibility of obtaining mean diastolic velocity from the distal LAD flow during DSE using contrast agents and harmonic imaging. The contrast agents can be used in difficult cases and can enhance the CF signals especially the systolic velocity.11

Our data demonstrate a good correlation between the quantitatively measured systolic WT by M-mode and the CFV and CFR (Fig. 2). Takeuchi et al.8 have also demonstrated a good correlation between the CFV and wall motion score index (WMSI) by visual assessment of RWMA from 2D imaging. They demonstrated a good correlation of CFV to the qualitatively obtained WMSI from 2D images. They have also demonstrated early blunting of CFR at 20mcg/kg/min stage in the group who developed RWMA at peak stress, whereas our data demonstrate that the CFR is attenuated even at a lower dose of 10mcg/kg/min (Table 4). This suggests that blunting of CFV at low dose dobutamine can detect ischemia earlier than the appearance of RWMA on 2D echo.

Significant decrease in WT by M-mode in group 2 at low dose dobutamine was a result of impaired CFR (Table 4). Only 10 patients had RWMA on 2D at peak DSE while 2D-guided M-mode demonstrated abnormal WT in 25 patients. This supports the additive benefit of measuring CFR during DSE to improve detection of myocardial ischemia. In early animal studies, a closely coupled relationship was noted between myocardial wall thickening and coronary flow, such that reduction in blood flow of around 10–20% were found to impair regional (but not global) wall thickening within an ischemic zone. The observed reduction in wall thickening was found to be proportional to severity of flow reduction, with greater degree of flow restriction causing greater severity in RWMA.12

The baseline CFV was high in group 2 patients who developed abnormal WT at peak stress (Table 4). This finding of abnormally high baseline CFV with attenuated CFR both at low dose and at peak dobutamine stress, along with reduced WT at low dose and peak dose dobutamine is suggestive of coronary artery disease of LAD. Increased CFV in LAD at the site of prior angioplasty was demonstrated by Hozumi et al.13 where the CFV was 60.3±21.2cm/s in patients who developed restenosis compassed to 35.1±7.6cm/s in patients with no restenosis. Ciati et al.14 reported that % coronary flow velocity increase >50% at the stenotic site are highly sensitive and specific for diagnosing significant stenosis.

The CFR has a high sensitivity compared to lower specificity in detecting ischemia as shown in our study and in previous studies which used DSE or coronary angiogram to detect CAD.5,15 This is due to the impairment of the CFR in both epicardial and microvascular CAD, but additional WT assessment beside CFV and CFR measurements during DSE will help in detecting significant CAD.


   Limitation of the study
Top
 Abstract
 Methods
 Results
 Discussion
 Limitation of the study
Clinical implication of this...
 Conclusion
 Notes
 References
 
The major limitation of our study is the lack of coronary angiography. Coronary angiography was not performed in our study patients since it was not indicated on clinical grounds. Furthermore, β-blockers, known to attenuate flow velocity response to dobutamine especially at low and intermediate doses was not discontinued prior to the DSE. This may underestimate the maximal CFR response to dobutamine.


   Clinical implication of this study
Top
 Abstract
 Methods
 Results
 Discussion
 Limitation of the study
 Clinical implication of this...
Conclusion
 Notes
 References
 
Our study demonstrated that CFV could be easily obtained during DSE. The relationship between CFR and M-mode derived systolic WT indicates that it can be used to detect ischemia early during DSE and may be more sensitive than RWMA observed on 2D imaging which usually develops at peak stress. The detection of myocardial ischemia by DSE can be improved if CFV and CFR measurements are added to the 2D assessment for RWMA.


   Conclusion
Top
 Abstract
 Methods
 Results
 Discussion
 Limitation of the study
 Clinical implication of this...
 Conclusion
Notes
 References
 
CFV and CFR assessments are feasible during DSE with second harmonic imaging without the need for contrast agent. CFR assessment during DSE improves the detection of myocardial ischemia.


   Notes
Top
 Abstract
 Methods
 Results
 Discussion
 Limitation of the study
 Clinical implication of this...
 Conclusion
 Notes
References
 
1 Tel.: +966 1 4777714x8840; fax: +966 1 4778771. Back

* Conflict of interest and financial disclosure: none. Back


   References
Top
 Abstract
 Methods
 Results
 Discussion
 Limitation of the study
 Clinical implication of this...
 Conclusion
 Notes
 References
 

  1. Hundley W.G., Lange R.A., Clarke G.D., Meshack B.M., Payne J., Landau C., et al. Assessment of coronary arterial flow and flow reserve in humans with magnetic resonance imaging. Circulation (1996) 93:1502–1508.[Abstract/Free Full Text]
  2. Miller D.D., Donohue T.J., Wolford T.L., Kern M.J., Bergmann S.R. Assessment of blood flow distal to coronary artery stenoses: correlations between myocardial positron emission tomography and poststenotic intracoronary Doppler flow reserve. Circulation (1996) 94:2447–2454.[Abstract/Free Full Text]
  3. Kozakova M., Palombo C., Pratali L., Bigalli G., Marzilli M., Distante A., et al. Assessment of coronary reserve by transesophageal Doppler echocardiography: direct comparison between different modalities of dipyridamole and adenosine administration. Eur Heart J (1997) 18:514–523.[Abstract/Free Full Text]
  4. Van Camp G., Ay T., Pasquet A., London V., Bol A., Gisellu G., et al. Quantification of myocardial blood flow and assessment of its transmural distribution with real-time power modulation myocardial contrast echocardiography. J Am Soc Echocardiogr (2003) 16:263–270.[CrossRef][Web of Science][Medline]
  5. Caiati C., Zedda N., Montaldo C., Montisci R., Iliceto S. Contrast enhanced transthoracic second harmonic echo Doppler with adenosine. A noninvasive, rapid and effective method for coronary flow reserve assessment. J Am Coll Cardiol (1999) 34:122–130.[Abstract/Free Full Text]
  6. Hozumi T., Yoshida K., Ogata Y., Akasaka T., Asami Y., Takagi T., et al. Noninvasive assessment of significant left anterior descending coronary artery stenosis by coronary flow velocity reserve with transthoracic color Doppler echocardiography. Circulation (1998) 97:1557–1562.[Abstract/Free Full Text]
  7. Hozumi T., Yoshida K., Akasaka T., Asami Y., Ogata Y., Takagi T., et al. Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography. Comparison with invasive technique. J Am Coll Cardiol (1998) 32:1251–1259.[Abstract/Free Full Text]
  8. Takeuchi M., Miyazaki C., Yoshitani H., Otani S., Sakamoto K., Yoshikawa J. Assessment of coronary flow velocity with transthoracic Doppler echocardiography during dobutamine stress echocardiography. J Am Coll Cardiol (2001) 38:117–123.[Abstract/Free Full Text]
  9. Guth B., Savage R., White F., Hagan A., Samtoy L., Bloor C. Detection of ischemic wall dysfunction: comparison between M-mode echocardiography and sonomicrometry. Am Heart J (1984) 107:449–457.[CrossRef][Web of Science][Medline]
  10. Alam M., Khaja F., Brymer J., Marzelli M., Goldstein S. Echocardiographic evaluation of left ventricular function during coronary artery angioplasty. Am J Cardiol (1986) 57:20–25.[CrossRef][Web of Science][Medline]
  11. Okayama H., Sumimoto T., Hiasa G., Morioka N., Yamamoto K. Usefulness of an echo-contrast agent for a assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery with transthoracic Doppler scan echocardiography. Am Heart J (2002) 143:668–675.[CrossRef][Web of Science][Medline]
  12. Vatner S.F. Correlation between acute reduction in myocardial blood flow and function in conscious dogs. Circ Res (1980) 40:201.
  13. Hozumi T., Yoshida K., Akasaka T., Asami Y., Kanzaki Y., Ueda Y., et al. Value of acceleration flow and prestenotic to stenotic coronary flow velocity ratio by transthoracic color Doppler echocardiography in noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol (2000) 35:164–168.[Abstract/Free Full Text]
  14. Caiati C., Montaldo C., Zedda N., Montisci R., Ruscazio M., Lai G., et al. 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. J Am Coll Cardiol (1999) 34:193–200.
  15. Hildick-Smith David J., Maryan Richard, Shapiro Leonard M. Assessment of coronary flow reserve by adenosine transthoracic echocardiography: validation with intracoronary Doppler. J Am Soc Echocardiogr (2002) 15:984–990.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ahmari, S. A.L.
Right arrow Articles by Chandrasekaran, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ahmari, S. A.L.
Right arrow Articles by Chandrasekaran, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?