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2. Indo-Am. J. Pharm & Bio. Sc., 2019 ISSN 2347-2251 www.iajpb.com
Ischemic and Non-Ischemic Heart Disease: A Patient-Specific Approach to
Scar Detection Using Cardiac MRI
B.Padmasri1
, P. Banujirao2
, V. Anil Kumar3
, R. Kalyani4
Abstract
The purpose of this research was to examine the use of cardiac magnetic resonance (CMR) feature tracking for scar identification in
a population of patients with varying degrees of ischemic and non-ischemic heart disease.
A total of 89 individuals with chronic ischemia and non-ischemic heart disease (IHD+) and 65 patients with ischemic scars
exclusively (IHD) had their cardiac magnetic resonance imaging (CMR) studies retrospectively analyzed. In all cases, original cine
pictures were processed using specialized software (Segment CMR, Medviso) to extract global (GCS) and segmental (SCS)
circumferential strain. Segmental values from GCSmedian percentage plots were associated with corresponding myocardial
segments in late gadolinium enhancement (LGE) after patient-specific median GCS (GCSmedian) was calculated.
Overall, the results showed a range of -3.5% to -19.8% in GCS, with a significantly lower average GCS in IHD+ compared to IHD
(p 0.05). The percentage of infarcted myocardial segments was 19% in IHD and 16% in IHD+. 6.7% of IHD+ segments also showed
evidence of non-ischemic LGE. GCSmedian percentage plots correlated with LGE to reveal that below a cut- off of 39.5%
GCSmedian (87.5% sensitivity, 86.3% specificity, AUC 0.907), the presence of ischemic scar tissue in a myocardial segment was
very probable.95% CI 0.875-0.938, p < 0.05).Ischemic scar tissue in the myocardium may be suspected using patient-specific
GCSmedian percentage plots computed from native cine pictures, as shown in the conclusion.
Keywords: Cardiac Magnetic Resonance; Feature Tracking; IschemicHeart Disease
List of Abbreviations: AHA- American Heart Association; AUC- Area Under The Curve; CMP- Cardiomyopathy; CMR-
Cardiac Magnetic Resonance; GCS- Global Circumferential Strain; GCSmedian- Patient-Specific Median Global Circumferential
Strain; HHD- Hypertensive Heart Disease; ICC- Intraclass Correlation Coefficient; IHD/IHD+- Chronic Ischemic Heart Disease/
Chronic Ischemic Heart Disease and Concomitant Non-Ischemic Heart Disease; LGE- Late Gadolinium Enhancement; LV- Left
Ventricle/ Left-Ventricular: LV-EDV- Left Ventricular End-Diastolic Volume; LV-EF- Left Ventricular Ejection Fraction; ROC-
Receiver Operating Characteristics;SCS- Segmental Circumferential Strain; SSFP- Steady- State Free Precession; T- Tesla
Introduction
Imaging scar tissue in ischemic heart disease has
progressed to the point where late gadolinium
enhancement (LGE) on cardiac magnetic resonance
(CMR) is a need [1]. Reduced diagnostic capability of
CMR scans in patients with ischemic heart disease and
contraindications to gadolinium mean that clinically
validated native approaches for identification of ischemia
scarring remain inadequate. By keeping tabs on previously
recorded voxels during the cardiac cycle, CMR feature
tracking detects myocardial deformation and gives
information on global and segmental strain from regularly
collected native cine sequences [2-4]. Reduced tissue
deformation characteristics in infarcts compared to strain
values of surrounding healthy myocardium led researchers
to conclude that segmental circumferential strain has great
potential for separating scar tissue from distant
myocardium [5-8]. Strain impairment is not exclusive to
ischemia damage; other cardiac illnesses, such as
cardiomyopathies and non-ischemic heart diseases, may
also affect strain values [9]. Furthermore, owing to inter-
individual heterogeneity in global strain levels, it is
difficult to define universally appropriate criteria for
infarcted and remote myocardium in heterogeneous patient
groups. This work thus explores a patient-specific method
to scar recognition, using a threshold based on median
global circumferential strain
1. B.Padmasri, Associate professor, Department of pharmaceutical Technology,
,Etcherla, Srikakulam.Email:padmasripharma@gmail.com
2.P. Banujirao, Assistant professor, Department of pharmacy Practice, Sri Venkateswara
College of pharmacy, Etcherla, Srikakulam.
3. V. Anil Kumar, Assistant professor, Department of pharmaceutical Technology, Sri
Venkateswara college of pharmacy, Etcherla, Srikakulam.
4. R. Kalyani, Assistant professor, Department of pharmacuetical Technology, Sri
Venkateswara college of pharmacy, Etcherla, Srikakulam

3. (
GCSmedian), in patients with ischemia and with both
ischemic and non- ischemic heart disease.
Methods
Study Population
The institutional review board and the local ethics
committee both gave their permission to this retrospective
investigation, and all patients who participated gave their
written informed consent. Between September 2017 and
January 2020, patients who visited our clinic for a CMR
check were analyzed for this research. Eighty-nine
individuals ("ischemic heart disease+" [IHD+]); Figure 1
out of 181 with chronic ischemic and non-ischemic heart
disease were included. These 89 individuals with ischemic
heart disease also had diagnoses of hypertension in an
additional 28, hypertrophy in an additional 23, LV
dilatation in an additional 26, and amyloidosis in an
additional 12 [10, 12]. Also recruited (Table 1) were 65
individuals from the same time period who had been
diagnosed with one of 85 chronic ischemic scars but no
other non-ischemic cardiac diseases ("ischemic heart
disease"/IHD). Patients who had recently had symptoms or
signs (acute chest pain, abnormal EKG, increased cardiac
enzymes, significant coronary stenosis on invasive
angiography) of a life-threatening cardiac disease were not
eligible for CMR.
89 patients with chronic ischemic and non-ischemic heart
disease were enrolled in the IHD+ group after 92 patients
were deemed ineligible due to exclusion criteria. This
group included 28 patients with hypertensive heart disease,
26 patients with severe left ventricular dilatation
(dilatative cardiomyopathy), 23 patients with hypertrophic
cardiomyopathy, and 12 patients with amyloidosis.
CMR Data Acquisition
All CMR exams were conducted on a clinical 1.5T
MR (Achieva, Philips Healthcare). Cine balanced
steady-state free precession (bSSFP) images in long-
axis geometries (2-, 3- and 4- chamber view) as well as
in short axis orientation covering the left ventricle
(LV) (field of view: 350 × 350
Figure 1: IHD+ group profile.
After exclusion of 92 patients, 89 patients with both chronic
ischemic and non-ischemic heart disease were enrolled in
IHD+ group: 28 patients with hypertensive heart disease, 26
patients with severe left ventricular dilatation (dilatative
cardiomyopathy), 23 patients with hypertrophic
cardiomyopathy and 12 patients with amyloidosis.
CMP: Cardiomyopathy; ED: End-Diastole/End-Diastolic; IHD+:
Patients with Concomitant Chronic Ischemic and Non-
Ischemic Heart Disease; LGE: Late Gadolinium
Enhancement; LV: Left Ventricle/Left-Ventricular; LV-EDV:
Left Ventricular End-Diastolic Volume; LV-EF: Left Ventricular
Ejection Fraction
mm2
; repetition time/echo time: 3.0/1.5 ms;
spatial resolutionSubsequently, percentages of
GCS
1.2 × 1.2 x 8 mm3
; number of cardiac phases: 50) were
acquired for functional LV assessment. After acquisition of
cine images,
Gadolinium (0.2 mmol gadobutrol [Gadovist; Bayer
Schering Pharma, Zurich, Switzerland] per kilogram
body weight) was applied for LGE sequences (inversion
recovery gradient-echo sequence; field of view: 350 × 350
mm2
; repetition time/echo time: 3.5/1.7 ms; spatial
resolution
1.2 × 1.2 x 8 mm3
; inversion time: 205–250 ms;
flip angle: 15°) in short axis orientation and in
2-,3- and 4 chamber view.

4. CMR Data Analysis
CMR feature tracking: Global (GCS) and segmental
(SCS) circumferential strain was derived from native cine
short axis stacks (anonymized data) using a specific software
(Segment CMR v3.0, Medviso; Figure 2) as previously
described [7] with both readers (M.P. and T.H.) being
blinded to each other, to patient information and to LGE
sequences. In every patient, patient- specific median GCS
(GCSmedian) was calculated from the segmental
circumferential strain values.
an individualized polar plot map (Figure 2d) and
segmental values were correlated with corresponding
myocardial segments in LGE short axis (reference
standard) [13].
Assessment of LV Function and LGE Images:
For the radiological report, ventricular volumes and
function were calculated using IntelliSpace Portal
(Philips, Version 8.0.3). LGE was classified as
“ischemic LGE” (subendocardial or transmural LGE
with accompanying regional wall motion abnormality)
or “non-ischemic LGE” (LGE in a midmyocardial,
epicardial or circular subendocardial/diffuse
distribution without concomitant wall motion
pathology). In ischemic LGE, segments with infarct
transmurality above 50% wall thickness were
considered “non-viable” [14]. Every CMR report was
revised by a EACVI level III cardiologist with > 20
years of experience in CMR (R.M.).
Statistical Analyses
Statistical analyses were conducted using commercially
available software (IBM SPSS Statistics, release 25.0;
Figure 2: 55-year-old male patient with chronic LAD infarction.
2a: Ischemic LGE in AHA segment 7,8,13 and 14 (red
arrows) in a 55-year-old patient with chronic ischemic heart
disease. 2b: Endo- and epicardial contouring of
corresponding cine short axis slices preceding strain
calculation (demonstrated by a basal, midventricular and
apical slice). 2c: Circumferential strain calculation with a
polar plot map depicting segmental values; mean GCS in
this patient is -6.6%. 2d: Based
on segmental strain values, patient-specific median GCS
(GCSmedian) was calculated and individual GCSmedian
percentage polar plot maps were generated. The resulting
percentage value of GCSmedian of every segment was
correlated with corresponding myocardial segment in LGE
short axis.
AHA- American Heart Association; GCS/SCS-
Global/Segmental Circumferential Strain; LAD- Left
Anterior Descending Coronary Artery; LGE- Late
Gadolinium Enhancement

5. Table 1: Patient characteristics of IHD and IHD+.
IHD
n = 65
IHD+
n = 89
p- value
Demographics
Female/male 24/41 42/47
Age (years) 62 ± 9 60 ± 12 0.3
BSA (m2) 1.9 ± 0.4 1.9 ± 0.7 0.8
BMI 27 ± 6 26 ± 4 0.5
LV morphology
LV-EDV [ml] 174 ± 22 185 ± 28 <0.05
LV-SV [ml] 93 ± 12 81 ± 15 <0.05
LV-EF [%] 53 ± 4 44 ± 10 <0.05
LV ischemic LGE (segments) 210 251 0.4
LAD 102 98 0.7
RCA 68 75 0.6
LCX 40 78 0.1
LV non-ischemic LGE (segments)
0 101
epicardial 4
midmyocardial 27
circular/diffuse 70
CMR LV strain
Average GCS (%; range) -16 ± 4 (-6.6 to -19.8) -12.9 ± 5 (-3.5 to -17.7) <0.05
Average SCS infarct (%; range) -5.9 ± 3 (2.3 to -7.3) -5.4 ± 2 (0.4 to -9.1) 0.5
Average SCS non-ischemic (%; range) - -11.8 ± 5 (-2.4 to -21.3)
Average SCS remote (%; range) -17.4 ± 5 (-11.5 to -22.8) -16.6 ± 4 (-6.5 to -19.1) 0.2

6. BSA- Body Surface Area; BMI- Body Mass Index; GCS/SCS-
Global/Segmental Circumferential Strain; LAD- Left Anterior
Descending Coronary Artery; LCX- Left Circumflex Artery;
LGE- Late Gadolinium Enhancement; LV-EDV- Left Ventricular
End-Diastolic Volume; LV-EF- Left Ventricular Ejection
Fraction; LV-SV- Left Ventricular Stroke Volume; RCA- Right
Coronary Artery
Figure 3: ROC curve for distinguishing infarcted and non-
infarcted myocardium based on percentage values of GCSmedian.
In segments with values below 39.5% patient-specific
median GCS (GCSmedian), ischemic scar can be assumed with
87.5 % sensitivity and 86.3% specificity (AUC 0.907 [95%
CI: 0.875 – 0.938, p < 0.05], Youden`s index 0.74). Infarcted
segments in LGE short axis stacks served as gold standard.
AUC- Area Under The Curve; GCS- Global
Circumferential Strain; GCSmedian- Patient-Specific Median
Global Circumferential Strain; LGE- Late Gadolinium
Enhancement; ROC- Receiver Operating Characteristics
SPSS, Armonk, NY). Categorical variables were expressed
as frequencies or percentages, continuous variables were
expressed as means ± standard deviations. Global and
segmental circumferential strain values were compared using
two-tailed paired t-tests or Wilcoxon signed rank tests. To
measure interobserver agreement, the intraclass
correlation coefficient (ICC) was used; ICC = 0.50- 0.75
was consideredmoderate, ICC = 0.75- 0.9 was
considered good and ICC
> 0.9 was considered excellent agreement [15]. Receiver
operating characteristics (ROC) were calculated and the
area
under the curve (AUC) was determined for the percentage of
Infarct Detection with GCSmedian Percentage Plots in
IHD and IHD+: Analysis of percentage plots of GCSmedian
calculated for every patient (IHD and IHD+) revealed a
cut- off value of 39.5% below the presence of ischemic
LGE in a segment had a sensitivity of 87.5% and
specificity of 86.3% (AUC 0.907, 95% CI 0.875-0.938, p
< 0.05; Figure 3, 4).
In segments with values below 39.5% patient-
specific median GCS (GCSmedian), ischemic scar
can be assumed with
87.5 % sensitivity and 86.3% specificity (AUC 0.907 [95%
CI: 0.875 – 0.938, p < 0.05], Youden`s index 0.74).
Infarcted
GCS to differentiate infarcted from remote
myocardium;segments in LGE short axis stacks
served as gold standard.optimal cut-off was
defined by the Youden’s index. A two-In some
IHD+ patients with GCS
below - 7%
sided p-value < 0.05 indicated statistical significance.
Results
Late Gadolinium Enhancement in IHD and
IHD+Ischemic Heart Disease (IHD): In IHD, 210 out of
1105segments(19%) had ischemic LGE; 194 of 210
infarcted segments (92.4%) were non-viable.
Concomitant Ischemic and Non-Ischemic Heart
Disease (IHD+): In IHD+, 251 out of 1513 (16.6%)
segments had ischemic LGE with mostly non-viable
infarcts (94%, 236 out of 251). Furthermore, 101
segments (6.7%) showed non- ischemic LGE. In patients
with hypertensive heart disease, 3 segments showed
midmyocardial LGE antero-/inferoseptal basal and 4
segments showed epicardial LGE at the basal RV
junction. In patients with dilatative cardiomyopathy, 15
segments show midmyocardial septal LGE.
Midmyocardial fibrosis was also found in 9 patients with
hypertrophic cardiomyopathy and 70 segments showed
circular/diffuseLGE in amyloidosis patients (Table 1).
Global Circumferential Strain
Among all patients (IHD and IHD+), individual GCS
ranged widely between -3.5% to -19.8%. IHD+ patients
had significantly lower average GCS than IHD patients (-
12.9% vs. -16%, p < 0.05; ICC 0.898, 95%CI: 0.832-
0.941). The lowest GCS was measured in patients with
cardiac amyloidosis (average GCS -9.7%, range from -
3.5% to -13.9%). Average GCS was higher in women
than in men(-15.4% vs. -14%, p < 0.05).
Segmental Circumferential Strain
Segmental Circumferential Strain in IHD and
IHD+: In IHD, average SCS was -17.4% (range -11.5 %
to -22.8%) in segments free of ischemic LGE, and -5.9%
(range: -2.3% to -7.3%) for ischemic LGE segments;
inter-reader agreement was extremely strong (ICC: 0.881,
95% CI: 0.823-0.932). SCS was on average -16.6%
(range: -6.5% to -19.1%) in IHD+ episodes without LGE.
Myocardial segments with ischemia LGE had a SCS of -
5.4% (range: 0.4% to -9.1%), whereas non-ischemic LGE
segments had a SCS of -11.8% (range: -2.4% to -21.3%).
We found a high level of agreement across readers (ICC
0.852, 95% CI 0.794-0.917).Eight infarcted segments had
values greater than the recommended threshold of 40%
GCSmedian (Figure 4), including three patients (2 with
amyloidosis and 1 with significant LV dilatation). Six of
the subendocardial scars that were still functional had
strain values greater than the
All of the segments were detectable in patients having
at least one segment below the 40% GCSmedian criterion.
Segment 17 was left out of the GCS calculation, making a
diagnosis of apical infarction impossible for 9 individuals.
Seven segments had ischemic LGE according to
GCSmedian criteria but showed no scar tissue on LGE
pictures; additional examination showed that strain
impairment in four of these segments was caused by an
LV diverticulum.

7. myocardial hibernation was most likely indicated by
the akinesia in 3 segments observed in short axis cine
without wall weakening. Finally, low values in 10
segments imply ischemia scar due to local aberrations in
the cine pictures, but there is no matching LGE or wall
motion abnormalities.
Discussion
Patients with chronic ischemia and non-ischemic heart
disease were included in this research to examine a patient-
specific strategy to employing CMR feature tracking for
native scar diagnosis. Ischemic scar tissue in a cardiac
segment could be identified with a sensitivity of 88% and a
specificity of 86% at a threshold of 40% patient-specific
median global circumferential strain (GCSmedian). CMR
feature tracking depicts global and segmental myocardial
deformation [16], and it is derived from regularly obtained
original cine pictures. Originating in echocardiography, this
technique is finding growing use in clinical CMR as a
means of gaining insight into the heart beyond what can be
gleaned from a visual assessment of wall motion [17].
Recent studies confirmed that local tissue destruction in
ischemic scars leads to significant local circumferential
strain impairment in contrast to adjacent
remote tissue, allowing to distinguish remote and infarcted
myocardium [5,6,18]. This is based on the premise that most
LV myocardial fibers are circumferentially orientated and
thus contribute to circumferential strain. As a result, this
method has the potential to increase the reliability of in-
house CMR tests for patients with ischemic heart disease
who cannot receive Gadolinium. However,
Figure 4: Influence of ischemic scar on segmental strain in IHD+
patients.
tic power of native CMR exams in patients who
decline contrast or have contraindications for
gadolinium. Hypertrophic cardiomyopathy (HCM) in a 53-
year-old female patient, showing diffuse mild
midmyocardial LGE in the anteroseptal basal and
inferoseptal midventricular regions (yellow arrows), as well
as transmural infarction in AHA segments 13-15. Infarcted
segments with GCSmedian values below 40% (15%, 17%,
and 18%, respectively), with the overall value being -17.7%.
A 65-year-old man patient was diagnosed with Dilated
Cardiomyopathy (DCM) based on his left ventricular
dilatation, decreased LV- EF (37%), and midmyocardial
septal thickening.
Transmural infarction in segments 10 and 15 and a low-grade
astrocytoma (LGE; yellow arrow) at the base. Infarcted segments
have values
of 11% and 8% of the median GCS below 40%.
Concentric left ventricular hypertrophy, extensive LGE in
the anterolateral and basal regions (yellow arrow), and a
significant ischemic scar in segments 7,8,13, and 14 are all
hallmarks of HHD in this 55-year-old male patient.
GCSmedian values in scar tissue are 23.0%, 19.0%, 29.0%,
and 27.0%.
This 62-year-old male patient has amyloidosis (yellow
arrow), which is characterized by widespread LGE, a very
low GCSmedian (-6.8%), and a tiny scar inferior lateral (red
arrow) with a GCSmedian percentage value of 47%, which is
higher than the suggested criterion of 40% GCSmedian.
GCS stands for global circumferential strain; PSGCS stands
for patient-specific median global circumferential strain;
AHA stands for the American Heart Association.
abbreviations for Left Ventricular Ejection Fraction (LV-EF) and
Late Gadolinium Enhancement (LGE)
Segmental circumferential strain has low specificity for scar
detection in the general population because it is affected by a
wide variety of conditions besides myocardial infarction,
such as inflammatory changes, cardiomyopathies, cardiac
infiltrative disease, and states like hibernating myocardium
[19–21]. With this in mind, we set out to identify a threshold
based on individual strain values, beyond which ischemia
scars might be predicted with high likelihood in patients with
chronic ischemic (IHD) and simultaneous ischemic and non-
ischemic heart disease (IHD+). No patient-specific studies
using CMR feature tracking for scar identification have been
published as of yet, to the best of our knowledge. When
looking at the complete sample, the average global
circumferential strain (GCS) was lower in IHD+ than in IHD
[16], but values varied from pathologically low (-3.5%,
patient with amyloidosis and infarction) to normal (-19.8%,
patient with modest ischemic scar). Interestingly, both
groups showed comparably low average segmental strain
values in infarcted segments. Local circumferential strain
was less severely impaired in non-ischemic LGE in IHD+
than in segments bearing ischemic scars. This is due to the
greater degree of LV wall damage induced by non-viable,
ischemic scars than by non-ischemic LGE, which has
generally intact wall integrity. GCSmedian % polar plots
may be readily created using patient-specific median GCS
(GCSmedian), which is more resilient to outliers than mean
GCS, and segmental circumferential strain data. A criterion
below 40% GCSmedian was shown to have 88% sensitivity
and 82% specificity in identifying the existence of ischemia
scar in a diverse patient population with a variety of heart
diseases using segment-wise correlation of the derived polar
plot values with LGE pictures. Only a small percentage of
infarcted regions had values greater than the recommended
threshold, and this was mostly seen in individuals with
substantially impaired GCS (below -7% GCS), such as those
with amyloidosis. Amyloidosis patients may have trouble
using LGE imaging to locate ischemia scars because diffuse
LGE might obscure otherwise visible lesions. Furthermore,
several functional infarcts produced false negative findings
with levels greater than the suggested cutoff. Due to identical
signal intensities between scar and surrounding myocardium
and relatively mild wall motion disturbance [22], viable scars

8. may be difficult to identify even in LGE. Additional capture
and assessment of T1 mapping, with likely greater local
values in infarcted tissue relative to surrounding distant
myocardium [23,24], might be one method to solving this
problem. Only a small number of false positives were
discovered, and those were mostly attributable to regional
anomalies. Apical infarction (section 17 of the AHA) could
not be determined in this study.
However, in cine long axis, SCS manifests as apical akinesia
or dyskinesia due to ischemia in the apex. To confirm that
the 40% GCSmedian threshold also applies to data computed
with other commercially available CMR feature tracking
tools, more research is needed as only one program was
utilized to generate global and segmentalcircumferential
strain. The suggested feature tracking approach might be
readily used in a prospective clinical scenario in patients with
known or suspected ischemic heart disease since cine
pictures are routinely obtained before contrast application.
Possible benefits include less gadolinium use in future CMR
tests and better diagnostic accuracy.
Conclusion
A threshold below 40% patient-specific median
global circumferential strain (GCSmedian) indicates
chronic scars in myocardial segments with a sensitivity
of 88% and a specificity of 86%. Since alternatives for
detecting scar tissue from native CMR exams are
limited, this patient-specific cine-based method could
help to improve diagnostic power of native CMR
exams
in patients with contraindication to Gadolinium.
However, in patients with severely reduced GCS, this
method might be not sensitive enough to detect
ischemic scars and additional use of tissue
characterization techniques should be considered.
Authors’ Contributions
M.P. provided the study concept. M.P. and O.M.
provided patient data and images. M.P. and T.H.
performed data analysis.
M.P. wrote the manuscript. H.A., S.K. and R.M. proofread
the manuscript.
Acknowledgements
Not applicable.
Source of Funding :
M.P. is financially supported by a grant
from thePromedica Foundation.
Competing Interests
The authors declare they have no competing interests.
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