it has been widely accepted that the application of coronary computed tomographic angiography ( ccta ) is most likely to benefit patients who are at intermediate risk of having stable coronary artery disease ( scad ) . as a result , in 2013 european society of cardiology guidelines on the management of scad ( 2013 g ) ,
importance was given to systematical testing with the consideration of pretest probability and the updated diamond - forrester model ( udfm ) was recommended as the clinical algorithm . according to 2013 g , ccta should be considered as an alternative to stress test in patients with ejection fraction ( ef ) 50% and pretest probability between 15% and 50% , or a complement to stress tests in patients with ef 50% and pretest probability between 50% and 85% or with ef < 50% and without typical angina .
the major expectation of the clinical guidelines was to establish a scientific basis for clinical practice .
however , 2013 g has not been subjected to systematic analyses on its impact on clinical practice .
therefore , the purpose of this study was to investigate the utilization of ccta in clinical practice and to determine the impact of 2013 g on the use of ccta .
from march 2013 to september 2014 , 5320 consecutive patients were eligible for the analysis .
the exclusion criteria were acute coronary syndrome , previous coronary revascularization ( percutaneous coronary intervention or coronary artery bypass grafting ) , impaired renal function ( serum creatinine > 120 mol / l ) , new york heart association class iii or iv heart failure , atrial fibrillation , aortic disease , or > 90 years old .
patients were considered to have diabetes mellitus , hyperlipidemia , or hypertension if they were taking corresponding treatment or had been diagnosed as such according to their medical records .
typical chest pain was defined as having ( 1 ) substernal chest pain or discomfort , which was ( 2 ) provoked by exertion or emotional stress and ( 3 ) relieved by rest and/or nitroglycerin .
if one or none of the criteria was present , the patient was classified as having nonangina associated chest pain .
all scans were performed with a second - generation dual - source ccta scanner ( somatom definition flash , siemens medical solutions , forchheim , germany ) .
patients received heart rate control , as well as sublingual nitroglycerin before ccta , and underwent prospectively electrocardiogram ( ecg)-triggered high - pitch spiral scan , step - on sequence , or retrospective spiral scan as appropriate .
two experienced observers , a radiologist and a cardiologist , evaluated the ccta data on a syngo multimodality workstation ( siemens medical solutions , forchheim , germany ) using volume rendering , multiplanar reformation and maximum intensity projection .
each segment was assessed for diameter , location , presence of atherosclerotic changes ( calcified and noncalcified ) , and concomitant coronary artery stenosis .
a significant stenosis was defined as an obstructive luminal reduction ( 50% ) compared with normal reference segment , while nonsignificance referred to mild stenosis ( < 50% ) . for each patient
appropriate ccta or appropriate stress test ( exercise ecg , stress echo , cardiac magnetic resonance , single photon emission computed tomography , and positron emission tomography ) was chosen as described in the 2013 g : ( 1 ) appropriate ccta - an alternative to stress tests for patients with ef 50% and pretest probability between 15% and 50% or a complement to stress tests for patients with ef 50% and pretest probability between 50% and 85% or with ef < 50% and without typical angina and ( 2 ) appropriate stress test - a preferred test for patients with ef 50% and pretest probability between 50% and 85% or patients with ef < 50% and without typical angina .
the trends in the half - monthly rate of appropriate ccta were examined across the following time periods : ( 1 ) prior to publication of the 2013 g ( march 1 , 2013 to september 1 , 2013 ) and ( 2 ) after the publication of the 2013 g ( september 1 , 2013 to september 1 , 2014 ) .
baseline differences between the time periods , as well as the conventional risk factors for scad , were adjusted using covariate analysis .
continuous variables were compared using students t - tests or mann  whitney u - tests as appropriate and were expressed as a mean  standard deviation ( sd ) .
count variables were expressed as frequencies with percentages and differences in the percentages were assessed using chi - square test or fisher 's exact test as appropriate .
analysis of the trends in the half - monthly rate of appropriate ccta within the time periods was performed using a generalized estimating equation model .
the model was adjusted for gender , age , the number of other risk factors , pretest probability , ef , appropriate stress test , patients ( admitted or out ) , and symptom .
wald chi - square tests were used to test the significance of the time trends .
from march 2013 to september 2014 , 5320 consecutive patients were eligible for the analysis .
the exclusion criteria were acute coronary syndrome , previous coronary revascularization ( percutaneous coronary intervention or coronary artery bypass grafting ) , impaired renal function ( serum creatinine > 120 mol / l ) , new york heart association class iii or iv heart failure , atrial fibrillation , aortic disease , or > 90 years old .
patients were considered to have diabetes mellitus , hyperlipidemia , or hypertension if they were taking corresponding treatment or had been diagnosed as such according to their medical records .
typical chest pain was defined as having ( 1 ) substernal chest pain or discomfort , which was ( 2 ) provoked by exertion or emotional stress and ( 3 ) relieved by rest and/or nitroglycerin .
if one or none of the criteria was present , the patient was classified as having nonangina associated chest pain .
all scans were performed with a second - generation dual - source ccta scanner ( somatom definition flash , siemens medical solutions , forchheim , germany ) .
patients received heart rate control , as well as sublingual nitroglycerin before ccta , and underwent prospectively electrocardiogram ( ecg)-triggered high - pitch spiral scan , step - on sequence , or retrospective spiral scan as appropriate .
two experienced observers , a radiologist and a cardiologist , evaluated the ccta data on a syngo multimodality workstation ( siemens medical solutions , forchheim , germany ) using volume rendering , multiplanar reformation and maximum intensity projection .
each segment was assessed for diameter , location , presence of atherosclerotic changes ( calcified and noncalcified ) , and concomitant coronary artery stenosis .
a significant stenosis was defined as an obstructive luminal reduction ( 50% ) compared with normal reference segment , while nonsignificance referred to mild stenosis ( < 50% ) .
appropriate ccta or appropriate stress test ( exercise ecg , stress echo , cardiac magnetic resonance , single photon emission computed tomography , and positron emission tomography ) was chosen as described in the 2013 g : ( 1 ) appropriate ccta - an alternative to stress tests for patients with ef 50% and pretest probability between 15% and 50% or a complement to stress tests for patients with ef 50% and pretest probability between 50% and 85% or with ef < 50% and without typical angina and ( 2 ) appropriate stress test - a preferred test for patients with ef 50% and pretest probability between 50% and 85% or patients with ef < 50% and without typical angina .
the trends in the half - monthly rate of appropriate ccta were examined across the following time periods : ( 1 ) prior to publication of the 2013 g ( march 1 , 2013 to september 1 , 2013 ) and ( 2 ) after the publication of the 2013 g ( september 1 , 2013 to september 1 , 2014 ) .
baseline differences between the time periods , as well as the conventional risk factors for scad , were adjusted using covariate analysis .
continuous variables were compared using students t - tests or mann  whitney u - tests as appropriate and were expressed as a mean  standard deviation ( sd ) .
count variables were expressed as frequencies with percentages and differences in the percentages were assessed using chi - square test or fisher 's exact test as appropriate .
analysis of the trends in the half - monthly rate of appropriate ccta within the time periods was performed using a generalized estimating equation model .
the model was adjusted for gender , age , the number of other risk factors , pretest probability , ef , appropriate stress test , patients ( admitted or out ) , and symptom .
wald chi - square tests were used to test the significance of the time trends .
all statistical analysis was performed by sas version 9.2 ( sas institute inc . , cary , north carolina , usa ) .
the baseline characteristics before and after the publication of 2013 g were compared [ table 1 ] .
the mean age of the patients and the proportion of women increased over time ( p = 0.0042 and 0.0096 , respectively ) .
more patients presented with angina pectoris ( 43.01% atypical angina and 23.66% typical angina ) , and this ratio was also elevated over time ( p = 0.0096 ) .
the number of patients receiving appropriate stress tests was small , although it increased markedly ( p < 0.0001 ) .
overall , 61.37% of patients received appropriate ccta , but there was no significant change over time ( p = 0.8701 ) .
the baseline clinical characteristics before and after the publication of 2013 g values are presented as mean  sd or n ( % ) .
* p<0.01 ; p<0.05 ; p<0.001 ; pretest probability for each patient was calculated using updated diamond - forrester method ; cad : coronary artery disease ; ef : ejection fraction ; ccta : coronary computed tomographic angiography ; sd : standard deviation .
details of the ccta procedural characteristics are summarized in table 2 . nearly , one - third ( 32.5% ) of the 5320 patients had at least one significant stenosis .
moreover , the multivessel disease was found in 15.9% of patients ( 2 vessels : 9.3% and > 2 vessels : 6.6% ) .
this proportion did not change over time ( p = 0.3451 ) , but a significant ( p < 0.05 ) decline was observed in complications , as well as radiation exposure .
ccta procedural characteristics before and after the publication of 2013 g values are presented as mean  sd or n ( % ) .*p<0.05 , p<0.01;. lm : left main ; lad : left anterior descending ; other lad included ramus intermedius , diagonal branch and middle and distal of lad ; lcx : left circumflex ; * * other lcx included posterior descending artery from lcx , posterior - lateral branch from lcx and middle and distal of lcx ; rca : right coronary artery ; other rca included posterior descending artery from rca , posterior - lateral branch from rca and middle and distal of rca .
ccta : coronary computed tomographic angiography ; sd : standard deviation . to investigate the rate of inappropriate ccta application ,
enrolled patients were sorted and compared according to different clinical risk levels [ figure 1 ] .
patients with ef 50% and pretest probability 15% , who were devoid of other complications , received more inappropriate cctas after 2013 g in comparison to those before 2013 g ( 16.3% vs. 13.9% , p = 0.0243 ) .
we observed a decrease in inappropriate use in patients with ef < 50% and without typical angina who should receive stress tests before ccta ( 2% vs. 3.3% , p = 0.0047 ) although there was no significant difference between these 2 time periods ( p = 0.0821 ) .
( a ) patients with ejection fraction 50% and pretest probability 15% should have other diseases excluded .
( b ) patients with ejection fraction 50% and pretest probability between 50% and 85% should take stress tests before coronary computed tomographic angiography .
( c ) patients with ejection fraction < 50% and without typical angina should take stress tests before coronary computed tomographic angiography .
( d ) for patients with ejection fraction < 50% and typical angina or ejection fraction 50% and pretest probability 85% , invasive coronary angiography was necessary .
the bars indicate the 95% confidence interval . in an analysis of appropriate ccta applications continuously ,
a nadir was found in the rate of appropriate ccta in may 2013 , 3 months prior to the publication of the 2013 g [ figure 2 ] . to avoid influencing the examination of trends in ccta within the time periods ,
the first time period was divided into two stages at the nadir ( march 1 , 2013 to may 1 , 2013 and may 1 , 2013 to september 1 , 2013 )
the rate of appropriate coronary computed tomographic angiography over the study period is shown for the overall study population .
furthermore , a significant decline was demonstrated in the adjusted rate of appropriate ccta [ figure 3 ] from the nadir on may 1 , 2013 to september 1 , 2014 ( odds ratio [ or ] for appropriate ccta per 15-day increase in time , 0.974 ; 95% confidence interval [ ci ] , 0.9600.987 ; p = 0.0002 ) .
however , there was no significant change before ( or , 0.989 ; 95% ci , 0.9581.021 ; p = 0.9683 ) or after ( or , 1.002 ; 95% ci , 0.9821.021 ; p = 0.8678 ) the publication of the 2013 g .
the ors referred to the adjusted odds of appropriate ccta in the interval of 15 days .
when subgroups were analyzed on the basis of gender , age , other risk factors , patients ( in - patient or out - patient ) , or symptom , no significant change was found in the adjusted rate of appropriate ccta following the publication of the 2013 g .
odds ratios for change in the rate of appropriate coronary computed tomographic angiography in different subgroups , per 15-day period .
the final model was adjusted for gender , age , number of other risk factors , pretest probability , ejection fraction , appropriate stress test , patients ( admitted and out ) , and symptom .
the baseline characteristics before and after the publication of 2013 g were compared [ table 1 ] .
the mean age of the patients and the proportion of women increased over time ( p = 0.0042 and 0.0096 , respectively ) .
more patients presented with angina pectoris ( 43.01% atypical angina and 23.66% typical angina ) , and this ratio was also elevated over time ( p = 0.0096 ) .
the number of patients receiving appropriate stress tests was small , although it increased markedly ( p < 0.0001 ) .
overall , 61.37% of patients received appropriate ccta , but there was no significant change over time ( p = 0.8701 ) .
the baseline clinical characteristics before and after the publication of 2013 g values are presented as mean  sd or n ( % ) .
* p<0.01 ; p<0.05 ; p<0.001 ; pretest probability for each patient was calculated using updated diamond - forrester method ; cad : coronary artery disease ; ef : ejection fraction ; ccta : coronary computed tomographic angiography ; sd : standard deviation .
details of the ccta procedural characteristics are summarized in table 2 . nearly , one - third ( 32.5% ) of the 5320 patients had at least one significant stenosis .
moreover , the multivessel disease was found in 15.9% of patients ( 2 vessels : 9.3% and > 2 vessels : 6.6% ) .
this proportion did not change over time ( p = 0.3451 ) , but a significant ( p < 0.05 ) decline was observed in complications , as well as radiation exposure .
ccta procedural characteristics before and after the publication of 2013 g values are presented as mean  sd or n ( % ) .*p<0.05 , p<0.01;. lm : left main ; lad : left anterior descending ; other lad included ramus intermedius , diagonal branch and middle and distal of lad ; lcx : left circumflex ; * * other lcx included posterior descending artery from lcx , posterior - lateral branch from lcx and middle and distal of lcx ; rca : right coronary artery ; other rca included posterior descending artery from rca , posterior - lateral branch from rca and middle and distal of rca .
to investigate the rate of inappropriate ccta application , enrolled patients were sorted and compared according to different clinical risk levels [ figure 1 ] .
patients with ef 50% and pretest probability 15% , who were devoid of other complications , received more inappropriate cctas after 2013 g in comparison to those before 2013 g ( 16.3% vs. 13.9% , p = 0.0243 ) .
we observed a decrease in inappropriate use in patients with ef < 50% and without typical angina who should receive stress tests before ccta ( 2% vs. 3.3% , p = 0.0047 ) although there was no significant difference between these 2 time periods ( p = 0.0821 ) .
( a ) patients with ejection fraction 50% and pretest probability 15% should have other diseases excluded .
( b ) patients with ejection fraction 50% and pretest probability between 50% and 85% should take stress tests before coronary computed tomographic angiography .
( c ) patients with ejection fraction < 50% and without typical angina should take stress tests before coronary computed tomographic angiography .
( d ) for patients with ejection fraction < 50% and typical angina or ejection fraction 50% and pretest probability 85% , invasive coronary angiography was necessary .
the bars indicate the 95% confidence interval . in an analysis of appropriate ccta applications continuously ,
a nadir was found in the rate of appropriate ccta in may 2013 , 3 months prior to the publication of the 2013 g [ figure 2 ] . to avoid influencing the examination of trends in ccta within the time periods
, the first time period was divided into two stages at the nadir ( march 1 , 2013 to may 1 , 2013 and may 1 , 2013 to september 1 , 2013 )
the rate of appropriate coronary computed tomographic angiography over the study period is shown for the overall study population .
furthermore , a significant decline was demonstrated in the adjusted rate of appropriate ccta [ figure 3 ] from the nadir on may 1 , 2013 to september 1 , 2014 ( odds ratio [ or ] for appropriate ccta per 15-day increase in time , 0.974 ; 95% confidence interval [ ci ] , 0.9600.987 ; p = 0.0002 ) .
however , there was no significant change before ( or , 0.989 ; 95% ci , 0.9581.021 ; p = 0.9683 ) or after ( or , 1.002 ; 95% ci , 0.9821.021 ; p = 0.8678 ) the publication of the 2013 g .
the ors referred to the adjusted odds of appropriate ccta in the interval of 15 days .
when subgroups were analyzed on the basis of gender , age , other risk factors , patients ( in - patient or out - patient ) , or symptom , no significant change was found in the adjusted rate of appropriate ccta following the publication of the 2013 g .
odds ratios for change in the rate of appropriate coronary computed tomographic angiography in different subgroups , per 15-day period .
the final model was adjusted for gender , age , number of other risk factors , pretest probability , ejection fraction , appropriate stress test , patients ( admitted and out ) , and symptom .
in this study , in patients subjected to ccta due to suspected scad , the rate of appropriate ccta was slightly more than 60% , and no significant change was found in this rate following the publication of the 2013 g .
our study indicated that there was a trend toward a decrease over time in the rate of ccta in some subgroups . despite the follow - up for 12 months following the publication of the 2013 g , inappropriate
ccta continued to be performed in a considerable proportion of patients suspected to have scad .
these findings suggested that the evidence provided by recent studies and the guideline recommendations have not been widely incorporated into clinical practice .
although reasons for the lack of impact of the 2013 g on clinical practice are multifactorial , the following one should emerge as a particularly strong candidate .
it has been investigated extensively that a pretest probability model developed in one population may overestimate or underestimate the probability in another population with different characteristics .
for example , several observations indicated a superior predictive accuracy of duke clinical score , but significant overestimations were observed by others .
udfm was the most efficient and operational model in the study of jensen et al .
, only revealing a moderate predictive accuracy . taking the limitations of the models into consideration , physicians were mainly concerned regarding the overestimation , which might lead to overuse of downstream tests and therapies . to improve acceptability of the pretest probability models in clinical practice , more rigorous external validations for the existing models
what is more , a standardized , reliable and easily usable model is more likely to contribute to promoting the application of guidelines in clinical practice . except for the belief that the model may overestimate the pretest probability ,
actually , nearly one in two inappropriate cctas resulted from the lack of appropriate stress tests , regardless of whether they were before or after the publication of 2013 g .
neither the class i recommendation (  should be considered  ) for stress tests as an initial test nor the class iia recommendation (  is recommended / is indicated  ) for ccta as a complement to stress tests in patients ( 1 ) with ef 50% and pretest probability between 50% and 85% or ( 2 ) with ef < 50% and without typical angina was widely incorporated into clinical practice .
although there is a general consensus that stress tests are more cost - effective than ccta in patients with a higher rate of intermediate risk , several speculative reasons accounted for the unsatisfactory use of stress tests , such as the lack of awareness , resources and reimbursement , and fear about the increase in malpractice liability .
the other major reason for inappropriate ccta was the overuse of ccta in patients with ef 50% and pretest probability 15% . according to the class iii recommendation (  is not recommendeds  ) in 2013 g
however , physicians are not inclined to alter their practice based on a negative recommendation , especially when it contradicts traditional beliefs and external influences , such as conflicting patient expectations , financial incentives , and fear of missed diagnosis .
all of these may play an important role in the development of the barriers between evidence and practice , but future studies may provide a more valuable explanation .
it is noteworthy that there are two different types of barriers :  overuse  and  underuse .
 this study only retrospectively included patients referred for ccta and focused on the  overuse  of ccta . according to the guideline recommendation , some patients who should have undergone ccta after an inconclusive stress test were referred directly to invasive angiography . more investigations are required to determine the  underuse  of ccta , which lead to  overuse  of invasive angiography in actual clinical practice .
first , while we strived to define a population that reflected the inclusion and exclusion criteria of udfm and 2013 g , there are considerable differences between the cohort in this study and others previously described .
the population in this study consisted of asymptomatic patients at risk for scad , such as patients with palpitation ( caused by arrhythmia rather than scad according to ecg ) and dizziness . instead of estimation of pretest probability , assessment of cardiovascular risk using  screening 
tests ( such as ecg , carotid ultrasound , and coronary calcium ) was recommended ( iia or iib ) and led to ccta overuse for these patients .
however , after sending them into the estimation of pretest probability , it resulted in an increase in the amount of appropriate ccta .
then , as a complement to stress tests in patients with a higher rate of intermediate risk , ccta was recommended after an inconclusive stress test . in this subgroup , we defined an appropriate ccta as one with a prior stress test , regardless of the conclusion .
as a result , an unnecessary ccta after a conclusive stress test was defined as an appropriate one .
finally , the influence of coronary artery calcification on ccta was not taken into consideration in this study .
although all of the limitations may lead to overestimation of the actual rate of appropriate ccta , they would have had no influence on the examination of trends in the rate of appropriate ccta .
although we collected data from a large , complex , and professional center , the impact of 2013 g in different centers , regions , and countries with different models of health care delivery and practice environments has not been assessed .
thus , a multicenter study with a large sample size will be needed in the future . in conclusion , this study found very little evidence that 2013 g has influenced practice in the subsequent 12 months .
the use of ccta as a  screening  test or an inappropriate alternative to a stress test remains commonplace despite little evidence to support it and new clinical practice guidelines recommending against it .
this study causes two main concerns : on one hand , it demonstrated that many patients suspected of scad continue to undergo a costly and ineffective ccta . on another hand ,
a huge investment in the generation of clinical evidence has yet to effectively influence clinical practice .
according to this study , a widely accepted method to estimate pretest probability and interventions in education , media campaigns , technical innovation , finance , multidisciplinary collaboration , and quality management may fundamentally improve this incomplete knowledge transfer .
this work was supported by grants from the national natural science foundation of china ( no .
this work was supported by grants from the national natural science foundation of china ( no .
 background : coronary computed tomographic angiography ( ccta ) has been widely used in patients who are at intermediate risk for having stable coronary artery disease ( scad ) , and 2013 european society of cardiology guidelines on the management of scad ( 2013 g ) recommended the appropriate application of ccta . however , 2013 g has not been subjected to systematic analyses for subsequent impact on clinical practice.methods:a total of 5320 patients suspected with scad were enrolled and scheduled for ccta from march 2013 to september 2014 . for each patient , 
 pretest probability of scad was calculated according to updated diamond - forrester model ( udfm ) . 
 appropriate ccta or appropriate stress test was determined as described in the 2013 g . 
 a generalized estimating equation model was used to determine the trends in the half - monthly rate of appropriate ccta.results:overall , only 61.37% of patients received appropriate ccta , and there was insignificant change over time ( p = 0.8701 ) . 
 the application of ccta in patients who should have had a stress test accounted for most of the inappropriate ccta before ( 22.29% ) or after ( 19.98% ) the publication of the 2013 g . in all patients or any subgroup , 
 no significant change in the adjusted half - monthly rate of appropriate ccta was found after the publication of the 2013 g ( odds ratio , 1.002 ; 95% confidence interval , 0.9821.021 ; p = 0.8678).conclusions : these findings suggest that the 2013 g have not , to date , been fully incorporated into clinical practice , and the clinical utilization of ccta remains unreasonable to some extent . 
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M
Study population and data collection
Coronary computed tomographic angiography
Data analysis
Statistical analysis
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Baseline characteristics of patients before and after 2013G
Coronary computed tomographic angiography application in patients before and after 2013G
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Financial support and sponsorship
Conflicts of interest