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European Heart Journal Advance Access published online on September 30, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn418
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

The value of fractional and coronary flow reserve in predicting myocardial recovery in patients with previous myocardial infarction

Branko Beleslin1,*, Miodrag Ostojic1, Ana Djordjevic-Dikic1, Vladan Vukcevic1, Sinisa Stojkovic1, Milan Nedeljkovic1, Goran Stankovic1, Dejan Orlic1, Natasa Milic2, Jelena Stepanovic1, Vojislav Giga1 and Jovica Saponjski1

1 Department for Diagnostic and Catheterization Laboratories, Clinical Center of Serbia, Institute for Cardiovascular Diseases, 8 Koste Todorovica, Belgrade, Serbia
2 Institute for Statistics, Medical School of Belgrade, 8 Dr Subotica, Belgrade, Serbia

Received 9 March 2008; revised 26 August 2008; accepted 29 August 2008.

* Corresponding author. Tel: +381 638328690, Fax: +381 113629056, Email: branko2801{at}eunet.yu


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Conclusions
 Funding
 References
 
Aims: The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the improvement of left ventricular (LV) function in patients with previous myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI).

Methods and results: Study population consisted of 46 patients (mean age 53 ± 7 years; 36 male) with previous MI and significant coronary stenosis undergoing PCI of infarct-related coronary artery. In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire during maximal hyperaemia before and immediately after PCI. We performed echocardiographic assessment of LV ejection fraction before and 6 months after PCI. Dobutamine stress echocardiography test was also performed before PCI. LV functional improvement was observed in 33/46 (72%) of patients. In patients with LV functional recovery in comparison with patients with no recovery, there was a significant difference in FFR before PCI (0.56 ± 0.14 vs. 0.70 ± 0.07, P < 0.001), improvement of FFR (0.35 ± 0.14 vs. 0.21 ± 0.07, P < 0.001), improvement of CFRthermo (1.3 ± 0.6 vs. 0.5 ± 0.3, P < 0.001), and CFRthermo after PCI (2.6 ± 0.7 vs. 2.0 ± 0.4, P < 0.001). When only parameters evaluated before PCI were taken into account, FFR before angioplasty (P = 0.001) and dobutamine-assessed viability (P = 0.006) were the most significant multivariate predictors of myocardial recovery. When all significant univariate parameters were evaluated, the most significant independent predictors for improvement in myocardial function were the improvement of CFRthermo during angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002).

Conclusion: Simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI. However, the evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization and may be used as an alternative to non-invasive testing.

Key Words: Fractional flow reserve • Coronary flow reserve • Myocardial infarction • Dobutamine stress echocardiography


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Conclusions
 Funding
 References
 
The evaluation of coronary pressure by fractional flow reserve (FFR) provides direct physiological and functional significance of coronary stenosis complementary to angiographic characterization.1–3 In fact, it has been shown that the correlation between FFR and diameter stenosis is weak, with large overlap particularly in patients with intermediate coronary stenosis, practically disabling the prediction of functional significance of coronary stenosis on the basis of angiography.4 The relation might be even more complex in patients with previous myocardial infarction (MI) where different amounts of necrotic and viable tissue influence myocardial perfusion area in a territory supplied by a stenotic coronary artery.

Diagnostic and prognostic significance of FFR has been mainly investigated in patients with normal left ventricular (LV) function, and data in patients with previous MI are mostly lacking.5,6 FFR is providing clinically useful diagnostic information both in patients with normal LV function as well as in patients with previous MI.5 In fact, the same cut-off value of 0.75 has been shown to be discriminative in both groups of patients,5 and thus, FFR may be used as an alternative to non-invasive testing for the provocation of myocardial ischaemia in establishing prompt, detailed, and proper indication for revascularization. However, similar concept has not been proved for the prediction of the improvement of myocardial function—i.e. the question remains on the relation between the improvement of FFR in patients with previous MI undergoing percutaneous coronary intervention (PCI) and the improvement in LV function in the follow-up period. We hypothesized that the improvement in functional indices during angioplasty (fractional and coronary flow reserve) will translate into the functional improvement of the left ventricle in patients with previous MI.

Therefore, the aim of this study was to evaluate the relation between FFR and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the functional improvement in LV function in patients with previous MI undergoing elective PCI. In addition, it was of further interest and clinical value to compare prognostic potential for the myocardial recovery of invasive functional parameters to accepted and well-known non-invasive method—dobutamine stress echocardiography test.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Conclusions
 Funding
 References
 
Study population
From November 2005 to January 2007, 51 patients with previous MI and significant coronary stenosis (≥50% diameter stenosis by QCA) detected by coronary angiography were initially included in the study. This was a prospective study with the inclusion of consecutive patients who fulfilled the following criteria: (i) previous first MI at least 7 days before the study; (ii) one-vessel coronary artery disease responsible for MI; (iii) echocardiographic identification of regional wall motion abnormalities corresponding to the site of MI and coronary lesion; and (iv) scheduled percutaneous intervention of infarct-related artery. As decision to perform PCI was based on the fulfilment of all inclusion criteria, but also the detection of FFR <0.80 at the time of scheduled percutaneous intervention of significant coronary stenosis in infarct-related artery, five patients deemed ineligible for inclusion after the initial assessment (FFR ≥ 0.80). Thus, the final study population consisted of 46 patients (mean age 53 ± 7 years; 36 male, 10 female). In addition, none of the patients with acute MI, multivessel coronary disease, occluded coronary artery, and absence of regional wall motion abnormalities were included in the study.

The study protocol was presented and approved by the Medical Ethical Committee of Clinical Center of Serbia, Belgrade, Serbia. Informed consent was obtained from all patients.

Echocardiographic evaluation
We have evaluated by echocardiography LV ejection fraction (biplane Simpson’s rule)7 and wall motion score index before and 6 months after the procedure (mean 6 ± 1 months). In all patients, we have also performed dobutamine stress echocardiography test for the evaluation of myocardial viability. Dobutamine was administered intravenously in successive doses of 5 and 10 µg/kg/min in 5 min intervals. Echocardiographic images were interpreted and analysed by an observer unaware of patients’ clinical, angiographic, and functional data. For the purpose of analysis, LV walls were divided into 17-segment model.7 Segmental wall motion was evaluated and scored as normal (score 1), hypokinetic (score 2), akinetic (score 3), and dyskinetic (score 4). A wall motion score index was derived by the summation of individual segment scores divided by the number of interpreted segments. High level of inter- and intraobserver reproducibility has been reported previously.8 Stress echocardiography test was considered positive for myocardial viability if the improvement in contractility and the thickening of infarcted segments were observed in at least two adjacent myocardial segments. LV functional improvement was defined as the improvement in contractility of at least two adjacent myocardial segments in the follow-up period.

Evaluation of fractional and coronary flow reserve during percutaneous coronary intervention
In all patients, we have evaluated by single pressure/thermo 0.014 in. guidewire (RADI) FFR and CFRthermo before and immediately after PCI. For PCI, a 6 or 7 F arterial sheath was introduced into the femoral artery. Adequate guiding catheter was positioned in the ostium of the respective coronary artery, and after the intracoronary administration of 200 mcg of nitroglycerine, angiogram of the coronary artery with stenosis was performed. After the heparinization of the patient, a guidewire, previously flushed and calibrated, was advanced to the tip of the guiding catheter to ensure identical pressures by the guiding catheter and pressure guidewire. The pressure wire was then passed across the stenosis and positioned into the distal part of the coronary artery. For the induction of maximal hyperaemia, we have used intracoronary administration of papaverine—15 mg for the left coronary artery and 10 mg for the right coronary artery. As we have evaluated simultaneously CFRthermo in addition to FFR, before inducing maximal hyperaemia, we have evaluated basal coronary flow in basal conditions by the intracoronary administration of 4 ccm of saline three times in succession. Then, maximal hyperaemia was induced, and during the plateau phase of papaverine action (stable minimal FFR), three additional saline boluses of 4 ccm were administered intracoronarily for the determination of peak coronary flow, presented as peak mean transit time. CFRthermo was calculated automatically and presented as a ratio of basal mean transit time and mean transit time during hyperaemia. After the evaluation of FFR and CFRthermo, we have proceeded to angioplasty using the same pressure wire. Immediately after successful angioplasty, we have performed, in identical manner as described previously, the evaluation of FFR and CFRthermo.

All angiographic images were analysed by dedicated system for quantitative coronary angiography (Siemens Quantcor qca). The images were analysed by an observer unaware of the patient clinical, functional, and echocardiographic data. After the visual inspection of the coronary artery, the frame of optimal clarity was selected, showing lesion at maximal narrowing and arterial silhouette in sharpest focus. After the calibration of guiding catheter, analysed arterial segment with coronary lesion was defined by moving the cursor from the proximal to the distal part of coronary artery to ensure adequate determination of reference diameter. We have measured minimal luminal diameter, reference diameter, per cent diameter stenosis, and length of the lesion. All measurements were repeated in the same view after angioplasty.

Statistical analysis
The data are expressed as mean ± standard deviation (SD). The sample size was determined for the estimated change in FFR during angioplasty of 0.10 or for the estimated change in coronary flow reserve during angioplasty of 0.5. With a population SD of 0.25, delta 0.40 (E/SD; E = 0.1), {alpha} error of 0.05, and 1-β = 0.80 (80% power of the study) calculated sample size was 50 patients. Normal distribution of all data was confirmed by the Kolmogorov–Smirnov test. Continuous variables were compared using Student's t-test for paired and independent groups. Dichotomous variables were compared using a {chi}2 test (McNemar's test for paired proportions). All tests were considered two-sided. Relation between angiographic, clinical, echocardiographic, and invasive physiological parameters was analysed by Pearson’s correlation coefficient.

A P-value <0.05 was considered statistically significant. However, {alpha}-adjustment according to the modified Bonfferoni's procedure was done to account for the inflation of the experiment-wise type I error due to multiple testing. Because we performed 40 consecutive statistical analyses, we choose a level of significance of {alpha} = 0.05/40 = 0.00125. A caution should be taken into account for the interpretation of the results between those two P-values.

Univariable logistic regression analysis was used to evaluate the relation between various clinical, echocardiographic, angiographic, and invasive physiological variables and improvement in the myocardial function in the follow-up period. To select covariates independently associated with the improvement in myocardial function, significant univariable predictors were reassessed by a multivariable logistic analysis, with values for inclusion and elimination set at P < 0.05. These variables are presented with P-values, odds ratio (OR), and 95% confidence intervals (95% CIs) for OR.

The receiver operating characteristic (ROC) analysis was used as an important tool for assessing the accuracy of diagnostic tests. When dealing with data measured on continuous measurement scales, it is often cumbersome to create and make an inference based on a non-parametric ROC curve. In order to determine the best cut-off value of FFR and CFRthermo for the differentiation of the improvement of myocardial function in the follow-up period, another approach to statistical inference—resampling method—was used.9,10 In the Results section, the validation by means of bootstrapping (computed over 1000 bootstrap samples) is presented. All measures of accuracy are presented with 95% CIs. Bootstrap percentile intervals ({alpha} and 1–{alpha} quantiles of estimated values) are presented as CIs from bootstrap samples.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Conclusions
 Funding
 References
 
Clinical characteristics of the patients are presented in Table 1. Anterior or anteroseptal MI was present in 30 patients (65%), and inferior or inferolateral MI in 16 patients (35%). Twenty-six patients (57%) received thrombolytic treatment in the early phase of MI. Maximal rise in creatine kinase was 1759 ± 1500 IU. Time from MI to PCI was 3.7 ± 6.3 months. During the study period, 35/46 patients (76%) were on β-blockers, 27/46 (59%) patients were on ACE-inhibitors, 35/46 patients (76%) were on statin therapy, and all the patients were on aspirin.


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  		Table 1 Clinical characteristics of the patients (n = 46)

 
The evaluation of FFR was successful in 45/46 patients (feasibility 98%), as in one patient the pressure wire could not cross the subocclusive lesion in circumflex coronary artery. The evaluation of CFRthermo was successful in 43/46 patents (feasibility 93%), as in additional three patients the variability of transit times during saline administration was too high (>20%), or mean resting transit time was too short (<0.25 s), disabling adequate values of CFRthermo during hyperaemia (RADI analyser does not measure shorter times than 0.11–0.12 s—therefore, in that case a CFR > 2 could not be obtained).

Angiographic and angioplasty data
Coronary lesions were successfully treated in all patients with the decrease of diameter stenosis from 63 ± 8 to 17 ± 8% (P < 0.001) and the increase of minimal luminal diameter from 1.14 ± 0.31 to 2.74 ± 0.55 (P < 0.001). Mean reference diameter was 3.1 ± 0.7 mm, and mean length of the lesion was 15 ± 7 mm. In 44/46 patients, coronary stents were implanted (two procedures were concluded only with balloon angioplasty). In 10/46 (22%) patients, drug-eluting stents were implanted, whereas in 34 patients bare metal stent(s) were implanted. Mean stent balloon diameter was 3.1 ± 0.4 mm, mean length of the stent was 21 ± 7 mm, and mean maximal balloon inflation pressure during intervention was 17 ± 2 atm. All the patients had TIMI 3 flow grade after angioplasty.

Fractional flow reserve and coronary flow reserve by thermodilution data: relation to clinical, echocardiographic, and angiographic variables
PCI induced significant improvement of invasive functional parameters (Figure 1). FFR increased significantly (P < 0.001) from 0.60 ± 0.14 (range 0.26 to 0.77) to 0.91 ± 0.06 (range 0.81–1.00). Mean improvement of FFR during coronary angioplasty (delta FFR) was 0.31 ± 0.14. Similarly, CFRthermo increased significantly (P < 0.001) from 1.4 ± 0.3 (range 1.0–2.0) to 2.4 ± 0.7 (range 1.2–4.7). Mean increase in CFRthermo (delta CFR) during coronary angioplasty was 1.0 ± 0.6.


Figure 1
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  		Figure 1 Fractional flow reserve and coronary flow reserve by thermodilution before and after angioplasty.

 
In regard to the relation between angiographic (% diameter stenosis, minimal luminal diameter) and invasive functional parameters, there was no significant correlation between them either before or after coronary angioplasty. However, there was a significant correlation between FFR and maximal creatine kinase (r = 0.47, P = 0.003) (Figure 2).


Figure 2
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  		Figure 2 Relation between fractional flow reserve and maximal creatine kinase.

 
Improvement in myocardial function
LV ejection fraction increased from 48 ± 6 to 56 ± 7% (P < 0.001), and wall motion score index decreased from 1.42 ± 0.24 to 1.26 ± 0.29 (P < 0.001). LV functional improvement was observed in 33/46 (72%) of patients. In patients with improvement in myocardial function, ejection fraction increased from 50 ± 6 to 58 ± 6% (P < 0.001), and wall motion score index decreased from 1.39 ± 0.22 to 1.17 ± 0.20 (P < 0.001). However, in patients with no improvement in regional function, ejection fraction was 46 ± 4% before angioplasty and 50 ± 9% in the follow-up period (P = 0.12), whereas wall motion score index was unchanged (1.50 ± 0.28 vs. 1.52 ± 0.35, P = 0.23). Myocardial viability by dobutamine stress echocardiography was present in 38/46 (83%) of patients, with positive predictive value for myocardial functional improvement in the follow-up period of 79% (30/38 patients) and negative predictive value of 63% (5/8 patients).

Table 2 presents differences in clinical, echocardiographic, angiographic, and invasive functional parameters in patients who have shown improvement in myocardial function in the follow-up period in comparison with those who have not. The improvement in myocardial function has been detected in patients with lower FFR before angioplasty, higher CFRthermo after angioplasty, as well as positive dobutamine stress echocardiography test and higher ejection fraction. However, higher improvement in FFR (delta FFR 0.35 ± 0.14 vs. 0.21 ± 0.07, P < 0.001) and CFRthermo during angioplasty (delta CFR 1.3 ± 0.6 vs. 0.5 ± 0.3, P < 0.001) were also associated with the improvement in myocardial function. There was no statistically significant difference between patients with and without improvement in myocardial function, in regard to data presented in Table 1, including risk factors and infarct-related artery. In addition, Figure 3 presents that the improvement in delta FFR and CFRthermo, but not the improvement in per cent diameter stenosis during angioplasty, was associated with the improvement in myocardial function in the follow-up period.


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  		Table 2 Clinical, angiographic, and functional invasive data in patients with and without improvement in myocardial function in follow-up

 

Figure 3
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  		Figure 3 Delta fractional flow reserve (fractional flow reserve after angioplasty minus fractional flow reserve before angioplasty), delta coronary flow reserve by thermodilution (coronary flow reserve by thermodilution after angioplasty minus coronary flow reserve by thermodilution before angioplasty), and delta diameter stenosis (% diameter stenosis before angioplasty minus % diameter stenosis after angioplasty) in regard to improvement in myocardial function in the follow-up period.

 
By bootstrapping resampling method, cut-off values of invasive functional parameters (Table 3), best predicting improvement in myocardial function, were FFR before angioplasty <0.71, improvement of FFR during angioplasty of >0.21, improvement of CFR during angioplasty of >0.80, and CFRthermo after angioplasty >2.0. When the values of FFR before angioplasty were categorized in regard to cut-off point of 0.71, positive predictive value of FFR before angioplasty for myocardial functional improvement in the follow-up period was 88% (29/33 patients) and negative predictive value was 69% (9/13 patients).


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  		Table 3 Cut-off values of invasive functional parameters best predicting improvement in myocardial function

 
Ideally, it would be of most interest to detect which patient will improve myocardial function before angioplasty. Therefore, we performed multivariable logistic regression analysis (Table 4) with entry probability of 0.05 for variables that were determined before angioplasty. FFR before angioplasty (P = 0.001) and dobutamine-assessed viability (P = 0.006) were the most significant multivariable predictors of myocardial recovery. Correct classification rate was 84.4%.


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  		Table 4 Multivariable regression analysis for all significant univariable variables predicting myocardial functional recovery

 
When multivariable regression analysis (Table 4) was performed for all significant univariable predictors, including improvement in CFRthermo and CFRthermo after angioplasty, the most significant independent predictors for the improvement in myocardial function were the improvement of CFRthermo during angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002), with correct classification rate of 90.7%. The value of improvement in FFR (delta FFR) during angioplasty was not taken into account in multivariable analysis because of high correlation (r = –0.90) and multicolinearity with the values of FFR before angioplasty.

Discussion
The evaluation of FFR and CFRthermo provides significant prognostic information on LV functional recovery in patients with previous MI undergoing elective PCI. This is the first publication to present that lower FFR before angioplasty, as well as higher improvement of FFR and CFRthermo, and higher CFRthermo after angioplasty are indicative of LV functional recovery in patients with previous MI. Therefore, we have proved our hypothesis that the improvement in functional parameters during angioplasty do translate into the functional improvement of the left ventricle in patients with previous MI. In addition, simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI.

Pathophysiological rationale: fractional flow reserve in myocardial infarction
It has been shown that basal and hyperaemic myocardial blood flow is reduced in infarcted regions in comparison with regions without MI.11,12 Claeys et al.13 have also shown that coronary blood flow velocity (corresponding to coronary flow reserve) for similar degree of coronary stenosis is smaller in infarcted regions than in regions without MI, both before and after angioplasty. Mechanisms responsible for the reduction in blood flow include reduced oxygen consumption in infarcted regions, inadequate dilation of epicardial and microvasculatory arterioles distally from the occlusion, ‘stunning’ of distal microcirculation, and partial obliteration of microvasculature.14 Pathophysiologically, and in regard to the evaluation of FFR and CFR, there are two main differences between myocardial regions with and without MI: myocardium mass, depending on coronary artery with stenosis, is smaller in spite of the same referent diameter of the coronary artery; and dysfunction of microcirculation. However, and most importantly, FFR takes into account those two pathophysiological consequences of MI. De Bruyne et al.5 have presented a remarkable schematic pathophysiological concept of the evaluation of FFR in patients with previous MI. In brief, for the same degree of coronary stenosis, functional significance of coronary stenosis for the regions with MI is less than for the same coronary stenosis in regions without MI, as viable myocardial mass is smaller. Consequently, FFR does not underestimate the functional significance of coronary stenosis; on the contrary, FFR in regions with MI takes into account both coronary stenosis and perfusion area of the coronary artery with residual stenosis. In other words, two anatomically identical stenoses have different functional significance if myocardial perfusion area is different. Our results, in regard to the correlation between FFR and maximal creatine kinase, further confirm the pathophysiological concept of the evaluation of FFR in patients with previous MI.

The value of functional indices in patients with previous myocardial infarction
De Bruyne et al.5 were the first to establish the role of FFR in patients with previous MI. However, Caymaz et al.15 comparing FFR in patients with and without MI have found significant differences, but have underestimated the role of FFR in patients with previous MI, concluding that it may not be a suitable and reliable method for the functional evaluation in infarcted patients. On the other hand, other authors16,17 finding no significant differences in FFR in patients with and without MI concluded that the method may be useful, but with no recognition of pathophysiology of FFR evaluation in patients with previous MI. Therefore, De Bruyne et al.5 have not only confirmed diagnostic value of FFR in patients with previous MI, but have provided pathophysiological explanation and background for functional evaluation in this group of patients. They have shown that the patients with positive SPECT imaging, in comparison with SPECT negative, have smaller FFR before angioplasty (0.52 ± 0.18 vs. 0.67 ± 0.16, P < 0.01) and significantly higher ejection fraction (63 ± 13 vs. 52 ± 10%, P < 0.01). In addition, they have found a weak but significant inverse correlation between ejection fraction and FFR (r = –0.29, P = 0.0495). The evaluation of FFR was performed in patients suffering MI ≥6 days, as it is suggestive that hyperaemic response is not the same in the acute phase of MI and during recovery.7 In fact, Wijns et al.18 have shown improvement in myocardial contractility and microcirculatory function in the early recovery period.

In comparison with previous reports, our data are not only in agreement with results of De Bruyne et al.5 but extends the value of FFR to prognostic potential, i.e. larger the MI area, higher the FFR, smaller the improvement of FFR during intervention, and smaller is the likelihood that the myocardial function will improve despite adequate and successful angioplasty. In addition, we have set different cut-off values of functional indices best differentiating patients who may improve myocardial function after successful angioplasty. Particularly, the cut-off value for FFR of 0.70 best discriminates patients who may improve myocardial function in the follow-up period.

The new aspect of this study is simultaneous evaluation of FFR and CFRthermo in patients with previous MI, demonstrating significant combined predictive value for the improvement in LV function. After experimental validation of CFRthermo,19 Pijls et al.20 have reported high feasibility of 87% and a very good correlation with Doppler-derived CFR (r = 0.80, P < 0.001). Finally, Barbato et al.21 have reported the results of the multicentre clinical trial of feasibility and applicability of CFRthermo in the ‘real world’ clinical practice. They have confirmed21 previous observation of high feasibility (93%) and a good correlation with Doppler-derived CFR (r = 0.79, P < 0.001). Nevertheless, both Doppler-derived CFR and CFRthermo suffer from the same limitations inherent to the concept of CFR that include dependence of haemodynamic conditions, dependence of basal coronary blood flow, and most importantly CFR cannot differentiate between epicardial stenosis and microvascular dysfunction. However, large multicentre trials have shown that Doppler-derived CFR have significant prognostic value in patients after angioplasty.22,23 Low CFR after angioplasty is a bad prognostic sign both for restenosis as well as for the improvement in myocardial function.22–24 Previous studies have also shown that coronary flow reserve before angioplasty identifies viable myocardium that will recover after revascularization.25 They have shown that in the ischaemic segments, a worsening of regional function was associated with no significant increase in regional flow, whereas in the viable segments, an increase in regional coronary flow was mirrored by an increase in the function of dyssynergic segments.25 Apart from procedural differences in relation to our study (PET allowing segmental evaluation of myocardial blood flow), our results in regard to the absence of CFR potential before angioplasty to detect myocardial segments that may improve are in fact concordant with previous findings, as most of our patients had viable but ischaemic myocardium. However, the improvement of CFRthermo during angioplasty and high CFRthermo after angioplasty are strongly associated with the improvement in myocardial function in the follow-up period.

Dobutamine stress echocardiography has proven value in the detection of viable myocardium.26 In this study, we have demonstrated comparable prognostic value of dobutamine stress echocardiography and FFR before angioplasty for the prediction of LV functional recovery in patients with previous MI undergoing successful angioplasty. Thus, FFR before angioplasty may be used as an alternative to dobutamine stress echocardiography for the prediction of myocardial recovery in patients already scheduled for diagnostic angiography and possible angioplasty. CFR gain after angioplasty increases prognostic potential, as demonstrated by our results, but has practical drawback that angioplasty has to be performed.

Study limitations
The study was performed in selected group of patients with previous first MI, one-vessel coronary artery disease responsible for MI scheduled for coronary angioplasty, and regional wall motion abnormalities corresponding to the territory of MI. The results of this study cannot be extrapolated to the patients with acute MI, as all the procedures with functional measurements were performed at least 7 days after MI in clinically stable patients.

The most critical issue in FFR and CFR measurement is the induction of maximal hyperaemia. In this study, we have used in all patients the intracoronary administration of papaverine for the induction of maximal hyperaemia. De Bruyne et al.27 have compared the hyperaemic effect of various vasodilatory stimuli and concluded that papaverine-induced maximal hyperaemia is comparable with adenosine according to FFR values. However, only papaverine intracoronary, as well as adenosine intravenously, induced constant and stable maximal hyperaemia (plateau phase) which started 23 ± 5 s after the initiation of administration and lasted for 22 ± 7 s. The other point during CFRthermo measurement was the occasional observation of high variability of the values of transit times, as well as very short transit times, that practically disable the adequate interpretation of data and the measurement of CFR. In such cases (three patients), the values of CFRthermo were excluded from further analysis. Nevertheless, the feasibility of FFR and CFRthermo were 98 and 93%, respectively, which is in agreement with previous reports.1,2,20,21 Compared with coronary flow reserve, a novel quantitative index of microvasculature function, the index of microcirculatory resistance, provides a more reproducible and specific assessment of the microcirculation, which is independent of haemodynamic conditions.28 In addition, Fearon et al.29 have shown that the index of microcirculatory resistance, evaluated in the setting of acute ST-segment elevation MI, was the only significant predictor of LV functional recovery. In our study, we have not separately evaluated the variability of FFR and coronary flow reserve. However, Ng et al.28 have previously demonstrated that the coefficient of variation between two baseline measurements was 18.6 ± 9.6% for CFRthermo, 6.9 ± 6.5% for the index of microcirculatory resistance, and 1.6 ± 1.6% for FFR.


   Conclusions
Top
 Abstract
 Introduction
 Methods
 Results
 Conclusions
Funding
 References
 
Ideally, coronary angiography in patients with previous MI should include the evaluation of myocardial ischaemia and myocardial viability at the same time and at the same place. Our data further extend the diagnostic value of the evaluation of FFR in patients with previous MI5 to prognostic potential. The evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization, and may be used as an alternative to non-invasive testing.


   Funding
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 Abstract
 Introduction
 Methods
 Results
 Conclusions
 Funding
References
 
This study was supported partially by the grant of the Ministry of Science of the Republic of Serbia.

Conflict of interest: none declared.


   References
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 Abstract
 Introduction
 Methods
 Results
 Conclusions
 Funding
 References
 

  1. Pijls NHJ, Van Son JAM, Kirkeeide RL, De Bruyne B, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous coronary angioplasty. Circulation (1993) 87:1354–1367.[Abstract/Free Full Text]
  2. Pijls NHJ, De Bruyne B, Peels K, Van Der Voort PH, Bonnier HJ, Bartunek J, Koolen JJ. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenosis. N Engl J Med (1996) 334:1703–1708.[Abstract/Free Full Text]
  3. De Bruyne B, Bartunek J, Sys SU, Heyndickx GR. Relation between myocardial fractional flow reserve calculated from coronary pressure measurements and exercise-induced myocardial ischemia. Circulation (1995) 92:39–46.[Abstract/Free Full Text]
  4. Bartunek J, Sys SU, Heyndrickx GR, Pijls NH, De Bruyne B. Quantitative coronary angiography in preciting functional significance of stenosis in an unselected patient cohort. J Am Coll Cardiol (1995) 26:328–334.[Abstract]
  5. De Bruyne B, Pijls NHJ, Bartunek J, Kulecki K, Bech JW, De Winter H, Van Crombrugge P, Heyndrickx GR, Wijns W. Fractional flow reserve in patients with prior myocardial infarction. Circulation (2001) 104:157–162.[Abstract/Free Full Text]
  6. Kern MJ, Lerman A, Bech JW, De Bruyne B, Eeckhout E, Fearon WF, Higano ST, Lim MJ, Meuwissen M, Piek JJ, Pijls NHJ, Siebes M, Spaan JAE. Physiological assessment of coronary artery disease in the clinical catheterization laboratory: a scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology. Circulation (2006) 114:1321–1341.[Abstract/Free Full Text]
  7. Lang RM, Bierig M, Devereux RB, Flachkampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ, Chamber Quantification Writing Group American Society of Echocardiography’s Guidelines and Standards Committee European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjuction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr (2005) 18:1440–1463.[CrossRef][Web of Science][Medline]
  8. Beleslin B, Ostojic M, Stepanovic J, Djordjevic-Dikic A, Stojkovic S, Nedeljkovic M, Stankovic G, Petrasinovic Z, Gojkovic Lj, Vasiljevic-Pokrajcic Z, Nedeljkovic S. Stress echocardiography in the detection of myocardial ischemia: head-to-head comparison of exercise, dobutamine, and dipyridamole tests. Circulation (1994) 90:1168–1176.[Abstract/Free Full Text]
  9. R Development Core Team. R: A Language and Enviroment for Statistical Computing (2008) Vienna: R Foundation for Statistical Computing.
  10. Sing T, Sander O, Beerenwinkel N, Lengauer T. ROCR: visualizing classifier performance in R. Bioinformatics (2005) 21:3940–3941.[Abstract/Free Full Text]
  11. Uren NG, Crake T, Lefroy DC, deSilva R, Davies GJ, Maseri A. Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction. N Engl J Med (1994) 331:222–227.[Abstract/Free Full Text]
  12. Maseri A, Crea F, Kaski JC, Crake T. Mechanisms of angina pectoris in syndome X. J Am Coll Cardiol (1991) 17:499–506.[Web of Science][Medline]
  13. Claeys MJ, Vrints CJ, Bosmans J, Krug B, Blockx PP, Snoeck JP. Coronary flow reserve during coronary angiopasty in patients with a recent myocardial infarction: relation to stenosis and myocardial viability. J Am Coll Cardiol (1996) 28:1712–1719.[Abstract]
  14. Pijls NHJ, de Bruyne B. FFR in some specific conditions. In: Coronary Pressure—Pijls NHJ, de Bruyne B, eds. (2000) 2nd ed. Dordrecht: Kluwer Academic Publishers. p247–270.
  15. Caymaz O, Tezcan H, Fak AS, Toprak A, Tokay S, Oktay A. Measurement of myocardial fractional flow reserve during coronary angioplasty in infarct-related and non-infarct related coronary artery lesions. J Invasive Cardiol (2000) 12:236–241.[Web of Science][Medline]
  16. Claeys MJ, Bosmans JM, Hendrix J, Vrints CJ. Reliability of fractional flow reserve measurements in patients with associated microvascular dysfunction: importance of flow on translesional pressure gradient. Catheter Cardiovasc Interv (2001) 54:427–434.[CrossRef][Web of Science][Medline]
  17. McClich JC, Ragosta M, Powers ER, Barringhaus KG, Gimple LW, Fisher J, Garnett J, Siadaty M, Sarembock IJ, Samady H. Effect of acute myocardial infarction on the utility of fractional flow reserve for the physiologic assessment of the severity of coronary artery narrowing. Am J Cardiol (2004) 93:1102–1106.[CrossRef][Web of Science][Medline]
  18. Wijns WJ, Vatner SF, Camici PG. Hibernating myocardium. N Engl J Med (1998) 339:173–181.[Free Full Text]
  19. De Bruyne B, Pijls NH, Smith L, Wievegg M, Heyndickx GR. Coronary thermodilution to assess flow reserve: experimental validation. Circulation (2001) 104:2003–2006.[Abstract/Free Full Text]
  20. Pijls NH, De Bruyne B, Smith L, Aarnaudse W, Barbato E, Bartunek J, Bech GJ, Van de Vosse F. Coronary thermodilution to assess flow reserve: validation in humans. Circulation (2002) 105:2482–2486.[Abstract/Free Full Text]
  21. Barbato E, Aarnoudse W, Aengerareven WR, Werner G, Klauss V, Bojara W, Herzfeld I, Oldroyd KG, Pijls NH, De Bruyne B, Week 25 Study Group. Validation of coronary flow reserve measurement by thermodilution in clinical practice. Eur Heart J (2004) 25:219–223.[Abstract/Free Full Text]
  22. Serruys PW, De Mario C, Piek J, Schroeder E, Vrints C, Probst P, de Bruyne B, Hanet C, Fleck E, Haud M, Verna E, Voudris V, Geschwind H, Emanuelsson H, Muhlberger V, Danzi G, Peels HO, Ford AJ Jr, Borsma E. Prognostic value of intracoronary flow velocity and diameter stenosis in assessing the short- and long-term outcomes of coronary balloon angioplasty: The DEBATE Study (Doppler Endpoints Balloon Angioplasty Trial Europe). Circulation (1997) 96:3369–3377.[Abstract/Free Full Text]
  23. Di Mario C, Moses JW, Anderson TJ, Bonan R, Muramatsu T, Jain AC, Suarez de Lezo J, Cho SY, Kern M, Meredith IT, Cohen D, Moussa I, Colombo A. Randomized comparison of elective stent implantation and coronary angioplasty guided by online quantitative angiography and intracoronary Doppler. DESTINY Study Group (Doppler Endpoint STenting INternational Investigation). Circulation (2000) 102:2938–2944.[Abstract/Free Full Text]
  24. Kern MJ, Donohue TJ, Aguirre FV, Bach RG, Caracciolo EA, Wolford T, Mechem CJ, Flynn MS, Chaitman B. Clinical outcome of deferring angioplasty in patients with normal translesional pressure-flow velocity measurements. J Am Coll Cardiol (1995) 25:178–187.[Abstract]
  25. Torres MA, Picano E, Parodi G, Sicari R, Veglia F, Giorgetti A, Marzullo P, Parodi O. Flow-function relation in patients with chronic coronary artery disease and reduced regional function: a positron emission tomographic and two-dimensional echocardiographic study with coronary vasodilator stress. J Am Coll Cardiol (1997) 30:65–70.[Abstract]
  26. Sicari R, Picano E, Landi P, Pingitore A, Bigi R, Colleta C, Heyman J, Casazza F, Previtali M, Mathias W Jr, Dodi C, Minardi G, Lowenstein J, Garyfallidis X, Cortigiani L, Morales MA, Raciti M. Prognostic value of dobutamine-atropine stress echocardiography early after acute myocardial infarction. Echo Dobutamine International Cooperative (EDIC) study. J Am Coll Cardiol (1997) 29:254–260.[Abstract]
  27. De Bruyne B, Pijls NHJ, Barbato E, Bartunek J, Bech JV, Wijns W, Heyndrickx GR. Intracoronary and intravenous adenosine 5'-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans. Circulation (2003) 107:1877–1883.[Abstract/Free Full Text]
  28. Ng MKC, Yeung AC, Fearon WF. Invasive assessment of the coronary microcirculation: superior reproducibility and less hemodynamic dependence of index of microcirculatory resistance compared with coronary flow reserve. Circulation (2006) 113:2054–2061.[Abstract/Free Full Text]
  29. Fearon WF, Shah M, Ng M, Brinton T, Wilson A, Tremmel JA, Schnittger I, Lee DP, Vagelos RH, Fitzgerald PJ, Yock PG, Yeung AC. Predictive value of the index of microcirculatory resistence in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol (2008) 51:560–565.[Abstract/Free Full Text]

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