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Coronary artery disease (CAD) is a major health problem worldwide asit carries high risk of developing heart failure, morbidity and mortality1.

 Left ventricular (LV) diastolicdysfunction is an early and sensitive marker of ischemia in patients with CAD, asit presents even before regional or global LV systolic dysfunction1-2 .Furthermore, it is well known that the atrium has an important role inmaintenance of LV stoke volume in the setting of LV dysfunction3.Evaluation of the LA function is emerging as an important component inassessing the effect of CAD on hemodynamics3.  Despite its vital contribution in cardiacfunction, assessment of atrial function is usually neglected in our routine dailypractice.

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During the cardiac cycle, the atria have three functions: reservoir,conduit and active contractile function4. Recently, several studies haveshown that strain (?) and strain rate (SR) are powerful parameters of deformation;they directly reflect both global and regional systolic and diastolic myocardialfunction 5-6, and can detect any early effects of CAD on LAfunctions7. The atrial reservoir function is reflected by systolicstrain and strain rates, and the conduit and contractile functions are reflectedby the early and late diastolic strain rate respectively8.  Atrialremodeling and atrial disease are associated with major adverse cardiovascularoutcomes especially atrial fibrillation, strokes and heart failure9-10.

  In this study we aimed to evaluate the function of bothatria in patients with CAD using strain and strain rate imaging, and correlatethis function with the severity of CAD.   Patients and methodsStudy design and population:We conducteda prospective, single center cohort studyfor 40 consecutive patients who presented to our department with chronic stableangina and were candidates for invasive coronary angiography. We enrolledpatients from December 2013 to May 2014, Patients were classified according to theseverity of CAD by coronary angiography into 3 groups; Group I with normalcoronary arteries (Gensini score = zero), Group II with mild CAD (Gensini score> 0 and < 20) and Group III with severe CAD (Gensini score ? 20). Allpatients were subjected to the following, full history taking, clinicalexamination and routine laboratory investigations, all demographic data and riskfactors of CAD were recorded; (age, sex, BMI, hypercholesterolemia (ongoingtreatment of hypercholesterolemia or serum cholesterol level either fasting or non-fasting> 200 mg/dl), diabetes mellitus (fasting serum glucose level > 126 mg/d or diabeticmedications) or currentcigarette smoking.Exclusioncriteria:To minimize theeffect of some medical conditions on the atrial function, we excluded the followinggroups of patients: elderly patients > 65 y of age, Obese patients with BMI ?30 kg/m2,acute coronary syndrome, any history of prior coronary artery revascularization(either surgical or through percutaneous catheterization), hypertensive patients(blood pressure >140/90 or being on antihypertensive medications), diabetesmellitus, patients with EF <55%, patients presenting with heart failure symptoms,  any form of valvular heart diseases, anyconduction system abnormality or rhythm other than sinus rhythm, severe renalor liver dysfunction and suboptimal echocardiographic images.EchocardiographyAll patient were subjected to full echocardiographic examinationsat rest, in the left lateral position using (Vivid E 9 dimension; GeneralElectric Medical Systems, Horten, Norway) equipped with 2.5-MHzvariable-frequency transducer).

Standard 2 D views, including, apical 4, apical2- chamber and parasternal long-axis views were obtained and apical views wereobtained also with color TDI modes. For data acquisition, 3 cardiac cycles werecollected and stored in a cine-loop format, to be processed using a software(Echo Pac, GE Vivid E9 echocardiography system version 113), for off-linemeasurements of TDI-based strain. Simpson method were obtained for assessmentof global LV systolic function, E/e’ ratio were obtained by Doppler assessmentof the mitral valve, E (early diastolic peak trans mitral flow velocity)divided by e’ which was measured through colour-coded TDI of the apical4-chamber view, using PW Doppler sample placed at the septal and lateral mitralannulus, then the average of both values was taken 11.1-     Calculation of Left and right atrial volume by biplane area lengthmethod:-         LAvolume = (0.

85 x Area 4ch x Area 2ch)/ (Longest LA length).  Both the LA long axis and LA area weremeasured in apical 2 and apical 4 chamber views at end of ventricular systole.The LA area was obtained: by tracing the endocardial border of the atriumexcluding pulmonary veins, LA appendage and sub annular plane. And LA long axiswas measured as a line extending perpendicular from the back wall of LA to themitral annular plane12.-         RAvolume = (0.85 x area 4ch x area 4ch)/ (RA length)”.where both RA lengthand RA area were measured in apical 4 chamber view at the end of ventricularsystole. RA area was obtained by tracing endocardial border of the right atriumexcluding tricuspid sub annular plane, RA appendage, IVC and SVC).

And RA longaxis was measured as a line extending from back wall of RA perpendicular to theannular plane of the tricuspid valve. (13)All atrialvolumes were indexed to the body surface area (BSA). BSA iscalculated by Mosteller formula: BSA (m2) = (Height (cm) x Weight (kg)/ 3600)½   14.-         Calculationof LA and RA distensibility using the following formula: (V max)- (V min) × 100/ (V min).      (V max) = maximal volume of the atrium at the end ofthe systole (T wave on ECG) & (V min) = minimum volume of theatrium at the end of the diastole (R wave on ECG) 12.2-     Strain and strain rate imaging of the left and right atrium:2D color-codedTissue Doppler  imaging (TDI), usingstandard apical 4 & apical 2 chamber views, at a high frame rate (>180fps) and the narrowest possible sector angel possible(30 °) images were bestored for offline analysis using Echo Pac, GE 113,  Atrial longitudinal systolic Strain S and SRwere measured by placing a  2 mm samplevolume (because of thin atrial wall) at the mid segment of : the LA septal wall, LA lateral wall, RA free wall (using  the apical 4 chamber view), and LA inferior walland LA anterior wall (using the apical 2 chamber view) 15,16. The studied segments were kept at the centerof the u/s sector to insure the accuracy, and strain S /SR velocity curves wereobtained and analyzed offline with dedicated software, atrial reservoirfunction during ventricular systole , represented by the interval betweenmitral valve closure (MVC) and mitral valve opening (MVO),peak positivesystolic strain and strain rate  werecalculated from the extracted curves over 3 recorded cardiac cycles to obtainmean strain and strain rate values of the studied segment.

(17)CoronaryAngiographyDiagnosticcoronary angiography was done to all patients through either femoral or radialapproach according to local protocol. Gensini score was used to assess theseverity of CAD by an experienced cardiologist, blinded to the echocardiographicdata of the patients. Gensini score was calculated through multiplication ofscore used for grading the luminal narrowing of the main coronary artery by afactor which takes into account the site and importance of the lesion. Thescore of luminal narrowing was 1 for ? 25 % stenosis, 2 for 26-50 % stenosis, 4for 51-75 % stenosis, 8 for 76-90 % stenosis, 16 for 91-99 % stenosis and 32for total occlusion.

The factor of location was 5 for left main, 2.5 for theproximal lesion of either LAD (left anterior descending) or LCX (left circumflex),1.5 for mid lesion, 1 for distal LAD, mid-distal LCX or RCA (right coronaryartery). Then the sum of scores of all coronary arteries was used to expressthe total Gensini score18.

 StatisticalAnalysis:SPSS software version 20 was used for statistical analysis. Thedata were analyzed using Student’s t-test and the numeric data were expressedas the mean ± SD. Categorical data were analyzed with a x2 test, and theresults were expressed in percentages.

ANOVA test was used for comparison amongdifferent times in the same group in quantitative data.   Chi-square test was used for comparisonbetween two groups as regards qualitative data. P<0.05 was consideredstatistically significant.ResultsThe 3 groupsincluded 10 patients with Gensini score =0 (group I), 15 patients with Gensiniscore < 20 (group II) and 15 patients with Gensini score ? 20 (group III). Demographicdata of group III (mean age: 51.0 + 6.

81 years, 10 (66.7 %) males, 9 (60%)smokers); In group II (mean age: 49.53 + 7.

12 years, 11 (73.3%) males ,10(66.7%) smokers, and in group I (mean age: 46.40+ 9.

59 years, 6 (60%) males, 8 (80%) non-smokers),CAD patients had significantly higher total cholesterol level  than the group with normal coronaries(p1=0.001 ,p2= 0.001)where p1;between group I and p2; between groupI& III .Also it was found that patients in group III have significantlyhigher LDL levels than group II (p3 =0.028) where p3; between group II& III(Table1).Echocardiographicmeasurements: (Table 2).As regard LV function, EF%values have no statistically significant difference in the three studied groups, the value of E/e’ in the 2 CAD groups was higher than the groupwith normal coronaries, but the differences didn’t reach statisticalsignificance.

E/e’ ratio was in the gray zone (between 5 to 13) representingthat there were no significant increase in LV diastolic filling pressure in thethree groups, None were found to have E/e’ > 15 (cut off value> 15represent elevated LV filling pressure (LVFP) 11. LA volumes(LA Vmin, LA Vmax) in the two groups having CAD werehigher than group I but they didn’t reach statistically significant difference(p value =0.272, 0.126) respectively. There was no statistically significantdifference between the three groups as regard LA diameter (p value =0.

986) norLA distensibility (p=0.243). There was no statistically significant differencebetween the three groups regarding RA volumes (RA V min, RA V max)and   RA distensibility. (Table 2)Deformation analysis As shown in Table 3, Mean LA S &SR showed decreased trend amongCAD patients less than normal coronary  group, also it was found that ( LA S&SR)measures correlated negatively with the severity of the CAD ( as it wasdecreased more in patients with Gensini score ? 20  than patients with Gensini score < 20.

). Meanleft atrial strain was higher in group I than group II & III. There wasstatistically significant difference between group I and II (p1=0.

001), betweengroup I and III (p2=0.001) & between group II & III (p3=0.005). Mean LAstrain rate was higher in group I than group II & III  , its average values  in group I , II  and III  were(2.95 + 0.

63,  1.81+ 1.23,   1.11 + 0.30) respectively, withstatistically significant difference between group I & II (p1 = 0.

002) ,between group I & III (p2=  0.001),also between group II & III ( p3= 0.041).

Mean RA strain was higher ingroup I than group II and III showing statistically significant differencebetween group I and II (p1=0.001) & between group I and III (p2=0.001), butthere was no statistically significant difference between group II & III(p3= 0.

083) (Figure 1). Mean RA SR was higher in group I than group II &III showing statistically significant difference between group I & II (p1=0.001),&between group I  and group III (p2=0.

001).But there was no statistically significant difference between group II & III(p3=0.748).

DiscussionThe atrium hasan important role in the overall cardiac function as it is acting as areservoir during LV systole, conduit during early LV diastole, and a boosterpump in late diastole, sharing up to 30% of LV stroke volume in normal subjects19.In CAD, the atrial function could be primarily or secondarily affected. Assessmentof LA and RA function may serve as an important component in the evaluation hemodynamiceffects of CAD20. In the presentstudy most of CAD patients were found to have elevated total cholesterol &LDL levels, also majority of CAD patients were smokers while in the group ofpatients with normal coronary angiography, only 20% were smokers. E/e’ was inthe gray zone (between 5 to 13) representing that there were no significantincrease in LV diastolic filling pressure in the three groups, None were foundto have E/e’ > 15 (  cut off value>15 represent elevated LV filling pressure (LVFP ) (21)and this mightminimize the effect of elevated LVEDP on atrial function.There was nostatistically significant difference between the three groups as regard LA andRA volumes and distensibility, all had normal LA dimension, on the other handpatients with CAD showed decreased LA and RA systolic strain (S) and strainrate (SR) measurements than the group with normal coronaries, also the presentstudy showed negative relation between LAs S(peak LA systolic strain) & LAs SR( peak LA strain rate ) and the severity of CAD. As regard tolipid profile the present study it comes in concordance with (Haddad et al) (22)who studied lipid profiles of 182 CAD patients and founded that there isincrease in total cholesterol, LDL and TG (triglycerides) in CAD patientscompared with the control group22. In the presentstudy, there was no statistically significant difference in LV EF % between the3 groups, furthermore the present study founded that LA volumes (LA Vmin, LAVmax) in the two groups having CAD were higher than group I but they didn’treach statistically significant difference, also as regard to LA dimensionthere was no statistically significant difference between the three groups,these results come in agreement with (Ping Yan et al.

) 23. Also it comesin agreement with (Liu Y, et al.) 24 who evaluate LA function inpatients with CAD ,using conventional echocardiographic and 2D strain andstrain rate  parameters, their resultsrevealed no statistically significant difference between control and CAD withnormal LA dimension groups as regard to LA volumes and this comes in agreementwith the current study . Meanwhile there was statistically significant increasein LA volumes in CAD with enlarged LA group than control group and this is notin agreement with the results of the current study.On the otherhand as regard to LA volumes the results of the current study are not inagreement with ( Yu M.C et al.) 25 They founded that there isincrease in LA cavity dimension and LA volumes in CAD patients than controlgroup with statistically significant difference between the two groups , In the presentstudy there was no statistically significant difference between the threegroups as regard RA volumes (RA Vmin, RA Vmax) and this is in agreement with(Yu M.C et al)25 results that showed no significant differencebetween CAD patients and control group as regard to RA volumes.

In the presentstudy, E/e’ was used together with LA distensibility to assess LV fillingpressure (LVFP) aiming to study its impact on LA function, as regard to E/e’ wefounded that the 2 CAD groups had higher E/e’ ratio when compared to the groupwith normal coronaries, but didn’t reach statistically significant difference,this is in agreement with (Ping Yan et al.) (23) .Furthermore asregard to E/e’, the result of the present study is not concordant with (Tsai etal) (26) who studied the diagnostic Value of Segmental LongitudinalStrain in Coronary Artery Disease without Left Ventricular Dysfunction, theyused tissue Doppler to obtain septal e’, they founded higher E/e’ ratio in CADpatients with preserved EF % than control groupAs regard LAdistensibility, results of the present study revealed no significant differencebetween the three groups, although there was no significant decrease in LAdistensibility in CAD groups compared to group I and this is comparable with(HSIAO SH et al.) 27 in their results  E/e’ was higher in multiple vessel group thansingle vessel groups and LA distensibility was lower in multiple vessel groupthan  single vessel group , and theyfounded that E/e’ is not completely satisfactory for assessing LVFP in patientswith stable angina, especially those with single-vessel disease & preservedsystolic function ,  average e’ was notsuperior to any regional e’ for assessing LVFP by the E/e’ method, and Foridentifying high LVFP in CAD patients, LA distensibility is better than E/e’. 28In the presentstudy, LA systolic strain (S)and strain rate(SR) measures show statisticallysignificant difference between the three groups, S& SR values weredecreased in CAD groups compared to the group with normal coronaries, and thisresult comes in agreement with (Liu, et al.

)24, they foundstatistically significant decrease in LA systolic S and SR measures in patientswith CAD compared to control group. This study concluded that, LA reservoirfunction in patients with CAD is impaired, even in the absence of LAenlargement. Also thisresult comes in agreement with (Guan et al.) 28 who studied the associationof  left atrial myocardial function withleft ventricular diastolic dysfunction in subjects with preserved EF% usingstrain and strain rate parameters, they enrolled 95 patients with differentstages of  LV diastolic dysfunction and29 normal subjects as control group, they founded that atrial  S and SR measures were reduced in patientswith mild and moderate diastolic dysfunction with E/e’  in gray zone (10.

2 ±  2.1and 12.1 ± 1.8 )   less than control group, with no change inatrial volumes or dimensions .Furthermore, asregard to LA strain and strain rate measures, the present study founded that LApeak systolic Strain and stain rate parameters were decreased in group III morethan group II with  statisticallysignificant difference giving negative relationship between the severity of CADand LA systolic S and SR, this result comes in disagreement with ( Ping Yan etal.)23  they founded thatthere was no significant difference between group with mild CAD and those withsevere CAD as regard to S and SR measures ,although in the same study LA S andSR showed decreased trend among CAD patients but didn’t reach statisticalsignificance when compared with control group and this also is not in agreement with the present study.

(23) Thisdisagreement may be explained by the difference in the exclusion criteria asthey enrolled diabetic and hypertensive patients in their study while weexcluded them and this may be important causes other than ischemia in affectionof LV diastolic function with subsequent impact on LA function.          As regard to RAsystolic S and SR measures the present study showed statistically significantdifference between CAD groups and group of normal coronaries, as CAD groupsshowed lower S and SR values, but between group II & III ( CAD patients)there was no significant difference, and this is not in agreement with ( PingYan et al.)23 results that revealed no significant differencebetween control ,and 2 CAD groups or even between 2CAD groups as regard to RA S& SR measurements, this may be explained by they used speckle trackingmethod while we used colored tissue Doppler to obtain S and SR measures ,alsowe didn’t stratify patients according to the distribution pattern of  the occluded vessel , so may be the majorityof the CAD patients in the present study had LCX and RCA occlusion that affect right atrial deformation measures throughatrial ischemia. Conclusion:CAD patientswith normal LA size, preserved EF and E/e’ in gray zone showed decreased  LA and RA systolic S and SR parameters withno difference in atrial volumes or distensibility and this  proves that atrial wall deformation occursearly in CAD even before any change in atrial volumes or dimensions hadoccurred. strain and strain rate echocardiographic imaging provides not onlymore sensitive markers for early detection of ischemia more than conventional echocardiographicmeasures , but also it may be used for detection of severity of CAD as LA S andSR were found to be more decreased in patients with Gensini score ? 20 thanthose with Gensini score  < 20.

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