Coronary of ischemia in patients with CAD, as it

Coronary artery disease (CAD) is a major health problem worldwide as
it carries high risk of developing heart failure, morbidity and mortality1.
 Left ventricular (LV) diastolic
dysfunction is an early and sensitive marker of ischemia in patients with CAD, as
it presents even before regional or global LV systolic dysfunction1-2 .
Furthermore, it is well known that the atrium has an important role in
maintenance of LV stoke volume in the setting of LV dysfunction3.
Evaluation of the LA function is emerging as an important component in
assessing the effect of CAD on hemodynamics3.  Despite its vital contribution in cardiac
function, assessment of atrial function is usually neglected in our routine daily
practice. During the cardiac cycle, the atria have three functions: reservoir,
conduit and active contractile function4. Recently, several studies have
shown that strain (?) and strain rate (SR) are powerful parameters of deformation;
they directly reflect both global and regional systolic and diastolic myocardial
function 5-6, and can detect any early effects of CAD on LA
functions7. The atrial reservoir function is reflected by systolic
strain and strain rates, and the conduit and contractile functions are reflected
by the early and late diastolic strain rate respectively8.  Atrial
remodeling and atrial disease are associated with major adverse cardiovascular
outcomes especially atrial fibrillation, strokes and heart failure9-10.  In this study we aimed to evaluate the function of both
atria in patients with CAD using strain and strain rate imaging, and correlate
this function with the severity of CAD.

 

 

Patients and methods

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Study design and population:

We conducted
a prospective, single center cohort study
for 40 consecutive patients who presented to our department with chronic stable
angina and were candidates for invasive coronary angiography. We enrolled
patients from December 2013 to May 2014, Patients were classified according to the
severity of CAD by coronary angiography into 3 groups; Group I with normal
coronary arteries (Gensini score = zero), Group II with mild CAD (Gensini score
> 0 and < 20) and Group III with severe CAD (Gensini score ? 20). All patients were subjected to the following, full history taking, clinical examination and routine laboratory investigations, all demographic data and risk factors of CAD were recorded; (age, sex, BMI, hypercholesterolemia (ongoing treatment of hypercholesterolemia or serum cholesterol level either fasting or non-fasting > 200 mg/dl), diabetes mellitus (fasting serum glucose level > 126 mg/d or diabetic
medications) or current
cigarette smoking.

Exclusion
criteria:

To minimize the
effect of some medical conditions on the atrial function, we excluded the following
groups 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), diabetes
mellitus, patients with EF <55%, patients presenting with heart failure symptoms,  any form of valvular heart diseases, any conduction system abnormality or rhythm other than sinus rhythm, severe renal or liver dysfunction and suboptimal echocardiographic images. Echocardiography All patient were subjected to full echocardiographic examinations at rest, in the left lateral position using (Vivid E 9 dimension; General Electric Medical Systems, Horten, Norway) equipped with 2.5-MHz variable-frequency transducer). Standard 2 D views, including, apical 4, apical 2- chamber and parasternal long-axis views were obtained and apical views were obtained also with color TDI modes. For data acquisition, 3 cardiac cycles were collected and stored in a cine-loop format, to be processed using a software (Echo Pac, GE Vivid E9 echocardiography system version 113), for off-line measurements of TDI-based strain. Simpson method were obtained for assessment of global LV systolic function, E/e' ratio were obtained by Doppler assessment of the mitral valve, E (early diastolic peak trans mitral flow velocity) divided by e' which was measured through colour-coded TDI of the apical 4-chamber view, using PW Doppler sample placed at the septal and lateral mitral annulus, then the average of both values was taken 11. 1-      Calculation of Left and right atrial volume by biplane area length method: -          LA volume = (0.85 x Area 4ch x Area 2ch)/ (Longest LA length).  Both the LA long axis and LA area were measured 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 atrium excluding pulmonary veins, LA appendage and sub annular plane. And LA long axis was measured as a line extending perpendicular from the back wall of LA to the mitral annular plane12. -          RA volume = (0.85 x area 4ch x area 4ch)/ (RA length)".where both RA length and RA area were measured in apical 4 chamber view at the end of ventricular systole. RA area was obtained by tracing endocardial border of the right atrium excluding tricuspid sub annular plane, RA appendage, IVC and SVC).And RA long axis was measured as a line extending from back wall of RA perpendicular to the annular plane of the tricuspid valve. (13) All atrial volumes were indexed to the body surface area (BSA). BSA is calculated by Mosteller formula: BSA (m2) = (Height (cm) x Weight (kg) / 3600)½   14. -          Calculation of 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 of the systole (T wave on ECG) & (V min) = minimum volume of the atrium 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-coded Tissue Doppler  imaging (TDI), using standard apical 4 & apical 2 chamber views, at a high frame rate (>180
fps) and the narrowest possible sector angel possible(30 °) images were be
stored for offline analysis using Echo Pac, GE 113,  Atrial longitudinal systolic Strain S and SR
were measured by placing a  2 mm sample
volume (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 wall
and LA anterior wall (using the apical 2 chamber view) 15,16.

 The studied segments were kept at the center
of the u/s sector to insure the accuracy, and strain S /SR velocity curves were
obtained and analyzed offline with dedicated software, atrial reservoir
function during ventricular systole , represented by the interval between
mitral valve closure (MVC) and mitral valve opening (MVO),peak positive
systolic strain and strain rate  were
calculated from the extracted curves over 3 recorded cardiac cycles to obtain
mean strain and strain rate values of the studied segment.(17)

Coronary
Angiography

Diagnostic
coronary angiography was done to all patients through either femoral or radial
approach according to local protocol. Gensini score was used to assess the
severity of CAD by an experienced cardiologist, blinded to the echocardiographic
data of the patients. Gensini score was calculated through multiplication of
score used for grading the luminal narrowing of the main coronary artery by a
factor which takes into account the site and importance of the lesion. The
score of luminal narrowing was 1 for ? 25 % stenosis, 2 for 26-50 % stenosis, 4
for 51-75 % stenosis, 8 for 76-90 % stenosis, 16 for 91-99 % stenosis and 32
for total occlusion. The factor of location was 5 for left main, 2.5 for the
proximal 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 coronary
artery). Then the sum of scores of all coronary arteries was used to express
the total Gensini score18.

 

Statistical
Analysis:

SPSS software version 20 was used for statistical analysis. The
data were analyzed using Student’s t-test and the numeric data were expressed
as the mean ± SD. Categorical data were analyzed with a x2 test, and the
results were expressed in percentages. ANOVA test was used for comparison among
different times in the same group in quantitative data.   Chi-square test was used for comparison
between two groups as regards qualitative data. P<0.05 was considered statistically significant. Results The 3 groups included 10 patients with Gensini score =0 (group I), 15 patients with Gensini score < 20 (group II) and 15 patients with Gensini score ? 20 (group III). Demographic data 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 group I& III .Also it was found that patients in group III have significantly higher LDL levels than group II (p3 =0.028) where p3; between group II& III (Table1). Echocardiographic measurements: (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 group with normal coronaries, but the differences didn't reach statistical significance. E/e' ratio was in the gray zone (between 5 to 13) representing that there were no significant increase in LV diastolic filling pressure in the three groups, None were found to have E/e' > 15 (cut off value> 15
represent elevated LV filling pressure (LVFP) 11. LA volumes
(LA Vmin, LA Vmax) in the two groups having CAD were
higher than group I but they didn’t reach statistically significant difference
(p value =0.272, 0.126) respectively. There was no statistically significant
difference between the three groups as regard LA diameter (p value =0.986) nor
LA distensibility (p=0.243). There was no statistically significant difference
between 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 among
CAD 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 was
decreased more in patients with Gensini score ? 20  than patients with Gensini score < 20.). Mean left atrial strain was higher in group I than group II & III. There was statistically significant difference between group I and II (p1=0.001), between group I and III (p2=0.001) & between group II & III (p3=0.005). Mean LA strain 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, with statistically 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 in group I than group II and III showing statistically significant difference between group I and II (p1=0.001) & between group I and III (p2=0.001), but there 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). Discussion The atrium has an important role in the overall cardiac function as it is acting as a reservoir during LV systole, conduit during early LV diastole, and a booster pump 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. Assessment of LA and RA function may serve as an important component in the evaluation hemodynamic effects of CAD20. In the present study most of CAD patients were found to have elevated total cholesterol & LDL levels, also majority of CAD patients were smokers while in the group of patients with normal coronary angiography, only 20% were smokers. E/e' was in the gray zone (between 5 to 13) representing that there were no significant increase in LV diastolic filling pressure in the three groups, None were found to have E/e' > 15 (  cut off value>
15 represent elevated LV filling pressure (LVFP ) (21)and this might
minimize the effect of elevated LVEDP on atrial function.

There was no
statistically significant difference between the three groups as regard LA and
RA volumes and distensibility, all had normal LA dimension, on the other hand
patients with CAD showed decreased LA and RA systolic strain (S) and strain
rate (SR) measurements than the group with normal coronaries, also the present
study showed negative relation between LAs S(peak LA systolic strain) & LA
s SR( peak LA strain rate ) and the severity of CAD.

As regard to
lipid 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 is
increase in total cholesterol, LDL and TG (triglycerides) in CAD patients
compared with the control group22.

In the present
study, there was no statistically significant difference in LV EF % between the
3 groups, furthermore the present study founded that LA volumes (LA Vmin, LA
Vmax) in the two groups having CAD were higher than group I but they didn’t
reach statistically significant difference, also as regard to LA dimension
there was no statistically significant difference between the three groups,
these results come in agreement with (Ping Yan et al.) 23.

Also it comes
in agreement with (Liu Y, et al.) 24 who evaluate LA function in
patients with CAD ,using conventional echocardiographic and 2D strain and
strain rate  parameters, their results
revealed no statistically significant difference between control and CAD with
normal LA dimension groups as regard to LA volumes and this comes in agreement
with the current study . Meanwhile there was statistically significant increase
in LA volumes in CAD with enlarged LA group than control group and this is not
in agreement with the results of the current study.

On the other
hand as regard to LA volumes the results of the current study are not in
agreement with ( Yu M.C et al.) 25 They founded that there is
increase in LA cavity dimension and LA volumes in CAD patients than control
group with statistically significant difference between the two groups ,

In the present
study there was no statistically significant difference between the three
groups 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 difference
between CAD patients and control group as regard to RA volumes.

In the present
study, E/e’ was used together with LA distensibility to assess LV filling
pressure (LVFP) aiming to study its impact on LA function, as regard to E/e’ we
founded that the 2 CAD groups had higher E/e’ ratio when compared to the group
with normal coronaries, but didn’t reach statistically significant difference,
this is in agreement with (Ping Yan et al.) (23) .Furthermore as
regard to E/e’, the result of the present study is not concordant with (Tsai et
al) (26) who studied the diagnostic Value of Segmental Longitudinal
Strain in Coronary Artery Disease without Left Ventricular Dysfunction, they
used tissue Doppler to obtain septal e’, they founded higher E/e’ ratio in CAD
patients with preserved EF % than control group

As regard LA
distensibility, results of the present study revealed no significant difference
between the three groups, although there was no significant decrease in LA
distensibility 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 than
single vessel groups and LA distensibility was lower in multiple vessel group
than  single vessel group , and they
founded that E/e’ is not completely satisfactory for assessing LVFP in patients
with stable angina, especially those with single-vessel disease & preserved
systolic function ,  average e’ was not
superior to any regional e’ for assessing LVFP by the E/e’ method, and For
identifying high LVFP in CAD patients, LA distensibility is better than E/e’. 28

In the present
study, LA systolic strain (S)and strain rate(SR) measures show statistically
significant difference between the three groups, S& SR values were
decreased in CAD groups compared to the group with normal coronaries, and this
result comes in agreement with (Liu, et al.)24, they found
statistically significant decrease in LA systolic S and SR measures in patients
with CAD compared to control group. This study concluded that, LA reservoir
function in patients with CAD is impaired, even in the absence of LA
enlargement.

Also this
result comes in agreement with (Guan et al.) 28 who studied the association
of  left atrial myocardial function with
left ventricular diastolic dysfunction in subjects with preserved EF% using
strain and strain rate parameters, they enrolled 95 patients with different
stages of  LV diastolic dysfunction and
29 normal subjects as control group, they founded that atrial  S and SR measures were reduced in patients
with 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 in
atrial volumes or dimensions .

Furthermore, as
regard to LA strain and strain rate measures, the present study founded that LA
peak systolic Strain and stain rate parameters were decreased in group III more
than group II with  statistically
significant difference giving negative relationship between the severity of CAD
and LA systolic S and SR, this result comes in disagreement with ( Ping Yan et
al.)23  they founded that
there was no significant difference between group with mild CAD and those with
severe CAD as regard to S and SR measures ,although in the same study LA S and
SR showed decreased trend among CAD patients but didn’t reach statistical
significance when compared with control group 
and this also is not in agreement with the present study.(23) This
disagreement may be explained by the difference in the exclusion criteria as
they enrolled diabetic and hypertensive patients in their study while we
excluded them and this may be important causes other than ischemia in affection
of LV diastolic function with subsequent impact on LA function.         

As regard to RA
systolic S and SR measures the present study showed statistically significant
difference between CAD groups and group of normal coronaries, as CAD groups
showed lower S and SR values, but between group II & III ( CAD patients)
there was no significant difference, and this is not in agreement with ( Ping
Yan et al.)23 results that revealed no significant difference
between 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 tracking
method while we used colored tissue Doppler to obtain S and SR measures ,also
we didn’t stratify patients according to the distribution pattern of  the occluded vessel , so may be the majority
of the CAD patients in the present study had 
LCX and RCA occlusion that affect right atrial deformation measures through
atrial ischemia.

Conclusion:

CAD patients
with normal LA size, preserved EF and E/e’ in gray zone showed decreased  LA and RA systolic S and SR parameters with
no difference in atrial volumes or distensibility and this  proves that atrial wall deformation occurs
early in CAD even before any change in atrial volumes or dimensions had
occurred. strain and strain rate echocardiographic imaging provides not only
more sensitive markers for early detection of ischemia more than conventional echocardiographic
measures , but also it may be used for detection of severity of CAD as LA S and
SR were found to be more decreased in patients with Gensini score ? 20 than
those with Gensini score  < 20.