Cardio Diabetes_2017 book

328 Cardio Diabetes Medicine 2017

Monitoring in Diabetes

Dr. Kevin Shotliff, UK

Consultant Physician, Diabetes and Endocrinology
Beta Cell Diabetes Centre

Chelsea and Westminster Hospital

London

Abstract: a test tube, then moving onto reagent strips which
are compared to a colour coded strip. The 1st com-
The use of self-monitoring methods by people with mercially available method being the Ames ‘Clinitest’
diabetes to help improve overall glycaemic control, launched in 1941, which used tablets added to urine
and in particular help reduce the day-to-day variabil- in a test tube, giving a chemical reaction and a co-
ity in glucose levels they experience, has progressed lour change depending on the glucose content of the
through many modalities, starting with urine test- urine. By 1954 Eli Lilly and Beohringer Manheim has
ing, then capillary blood glucose testing, and more launched Glucotest and the Testape roll, which were
recently the use of continuous glucose monitoring testing strips which were put into urine, with a colour
systems (CGMS), and is likely to progress further as change compared visually to a chart to determine the
technology advances. glucose level, before the more familiar Dipstix such
as Diastix and Clinistix became regularly used in the
Text: 1960’s.

It is now well accepted that the longer a person with This monitoring method relies on blood and renal
diabetes is exposed to high blood glucose levels, filtrate glucose levels exceeding the renal threshold
the great potential there is for them to develop both for resorption, typically around 10 mmol/L, but this
macrovascular and microvascular complications, as threshold can vary both between individuals, and
well as more acute metabolic issues from the elevat- also in the same individual over time, so is not ide-
ed blood glucose. The use of glycated haemoglobin al. It also gives an average of glucose levels for the
/ HbA1c measurements as a measure of glycaemic time urine accumulates in the bladder, rather than
control over the preceding 2 to 3 months, with the the absolute value at a particular point in time, but
month prior to the sample taken being particularly is much better than the historical method of tasting
important in that value, is also well accepted and urine for its sweetness.
standard practice, with individualised targets for
HbA1c levels in different patient groups ‘now been Blood glucose measurements, initially with
normal practice. This more intermediate term mea- strips,again being compared to colour changes on
sure however, gives an overview of glycaemic con- a chart, often on the side of the container used to
trol, but not an idea of day to day variability. store the strips, started to be available from the mid
1960s, but were not really used for self monitoring
Self-monitoring by the person with diabetes of their until the late 1970’s and the first, more regular use
glycaemic control is one way to try and assess this of a self monitoring system, rather than a hospital
day to day variability, in more detail,and again is not based system, with a meter, was in the 1980’s, with
a new concept. Ideally access to this self-monitoring the first Roche Reflolux / Accu-chek meter available
data allows an individual to adjust their diet exercise in 1983. By the late 1980’s second generation meters
and glucose lowering therapy enough to achieve bet- were available, and by the early 1990’s strips which
ter overall blood glucose control, so reducing the po- allowed capillary blood to be drawn into a gap be-
tential for hypoglycaemia associated complications. tween two plastic layers of a test strip, nearer to the
technology we take for granted now, started to be-
Home urine glucose measurements have been used
for many years, initially using a chemical reaction in

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Monitoring in Diabetes 329

come available. and iPhones. This more accessible data, allows the
opportunity to set alarms for high and low blood
These capillary blood glucose level electronic meters, glucose levels, and for the sharing of results. The
with the use of lancet devices to pierce the skin have Dexcom 5 system for example has a facility to do
therefore become the typical self-monitoring modal- this and to also upload to a ‘cloud’ and so make the
ity used in most patients, who need to do this. The data available to other users, such as medical staff,
frequency and timing of these measurements, again to allow further manipulation and adjustment of ther-
being tailored to the individual, and their needs. apy and other parameters to help improve glycaemic
control further, or to look at changes to help reduce
Continuous glucose monitoring systems (CGMS) detrimental aspects such as hypoglycaemia.
have more recently become available, with the first
devices available from 2006. These devices rely on Sensors such as the Medtronic Enlite glucose sen-
insertion of a sensor through the skin to measure sor, can also link into insulin pumps, and allow for
subcutaneous or interstitial fluid, which is used as a potential closed loop system, so also looking to
a measure of the equivalent blood on capillary glu- improve glycemic control.
cose levels, allowing for more frequent if not contin-
uous testing, to filling gaps between the single point It should however be remembered that subcutaneous
measurements taken using capillary blood glucose or interstitial fluid measurements are not the same as
monitoring systems. These systems typically mea- capillary or venous measurements, with a delay of
sure glucose levels every 5 minutes, so giving almost 5 to 20 minutes often quoted between the capillary
290 single measurements each day, to allow better and interstitial result. If a patient therefore feels they
understanding of any trends or patterns in blood glu- are experiencing a hypoglycaemic episode, capillary
cose level over time. The initial devices, stored data blood glucose testing is a better way of knowing
over the lifetime of the probe, typically a few days, whether they are, than CGMS, although the latter
which could then be downloaded and analysed, and could give them an idea of the rate and timing of
if reviewed in conjunction with the patient completed any change in their blood glucose levels. This may be
diary, used to suggest any changes needed in thera- particularly useful the nocturnal and daytime hypo-
py. These are sometimes called ‘blinded’ CGM where glycaemic episodes, when hypoglycaemic awareness
data is saved for subsequent clinic review and not is not present. Several systems also require capillary
visible to the user, compared to ‘real time’ for open blood glucose measurements the calibration, al-
CGM where readings are provided on demand the though the latest generation sensors are reach the
patient who can use them to adjust their treatment. point where calibration measurements are not rou-
tinely required.
More recent systems, include Flash Glucose Mon-
itoring Systems, such as the Freestyle Libre, from A further advance in CGMS is the use of implant-
Abbott, which was launched in the UK in 2014, al- able sensors, that concurrently last up to 90 days,
though is not currently an NHS available product. such as the Ever sense CGM system, which has an
This has a topical disposable sensor, which is in the implantable sensor inserted under the skin, as a mi-
form of a patch which is stuck onto the skin, in which nor procedure with local anaesthetic, and an external
is found a sensor, which collects data of glucose lev- removable, rechargeable and water resistant smart
els in interstitial fluid, with 8 hours of data kept on transmitter, which can then be placed over the sen-
the sensor. This patch also contains a transmitter to sor. This transmitter can be set to vibrate for alerts.
allow this data to be collected onto a separate hand- The sensor receives its power / charge from the
held receiver, which is similar in size to many of the smart transmitter, and will not measure blood glu-
currently used capillary blood glucose meters on the cose levels when the transmitter is not being worn.
market. Data can be examined either on this hand-
held device, or downloaded onto the PC if needed. The transmitter uses Bluetooth technology to trans-
mit data collected to a smart phone for a more de-
Improvements in HbA1c, have been reported with this tailed evaluation of glucose levels. A 150 day version
type of monitoring, when compared to capillary blood of the sensor is potentially due for release in the near
glucose testing, but its current limited availability due future. The smart phone display allows the user to
to the need for self-funding may limits its usefulness look at rate and direction of change in glucose levels,
in our centre. and provides alerts when glucose approaches low or
high levels. Projective alert algorithms can also be
Newer devices on the market, also now include Blue- used to give advance warning of high-powered hy-
tooth technology which allows these devices to be poglycaemic events as well.
linked into compatible smart devices, such as iPads

Cardio Diabetes Medicine

330 Cardio Diabetes Medicine 2017

Summary

The advances in technology already available to
health care professionals, and the patients we look
after, does provide more data on which we can
base treatment regimens and the changes needed
to these, so trying to reduce the variability in blood
glucose levels experienced by people with diabetes,
avoiding both hyper and hypoglycaemia as much as
we can, and potentially helping to reduce the risk of
both macro and micro vascular complications.
Future advances may allow both sensing of glucose
levels and alteration in blood glucose lowering ther-
apy even more, to help those with diabetes to adjust
their therapy themselves, with the help of their health
care professionals, or to allow for these adjustments
to be calculated and undertaken through closed loop
systems, so helping to achieve better glycaemic con-
trol, and potentially reducing long-term complications
associated with poorer control.

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Cardio Diabetes Medicine 2017 331

Post Revascularisation Status - Myocardial
Perfusion Imaging

Dr.Shrikant Solav MD.,
DRM Nuclear Medicine
Consultant in Nuclear Medicine, Pune

Introduction : However, in individuals with coronary artery disease,
the resting perfusion is homogeneous due to laminar
Percutaneous revascularisation procedures have rev- flow and this becomes inhomogeneous under stress.
olutionized the field of interventional cardiology. When subjected to exercise test, there is dispropor-
tionate dilatation of healthy coronaries as compared
PAMI (Primary Angioplasty in Myocardial Infarction) to a segment supplied by a stenosed artery that re-
to elective multi-vessel angioplasty are being routine- sults in deprivation of adequate blood flow resulting
ly carried out in cardiac cathlabs. in perfusion defect.

Surgical revasculisation has also been refined over The procedure provides objective assessment of
the period of years to minimally invasive techniques territory wise ischemia. Thus, in a patient with angi-
thereby reducing the peri-operative morbidity. na,culprit vessels can be identified with confidence.

The purpose of all these procedures is to eliminate In the post revasculisation period, conventional stress
or minimize myocardial ischemia. test has limited value to identify restenosis.

Patients with typical angina need to be addressed However, myocardial perfusion study can detect the
with several questions. precise territory of ischemia/ restenosis.

1. Is the angina associated with left ventricular dys- Please note that MPI should be interpreted with cau-
function? tion in the immediate post PTCA status.

2. Is the angina responding to optimal medical treat- There are following patterns of abnormalities that can
ment? be seen to indicate restenosis:

3. Is the angina related to multi-vessel ischemia? OR 1. Reversible perfusion defect in a non-revascularised
territory- indicates new coronary disease.
4. Is the angina masked/ under estimated because
of co-morbidities such as diabetes? 2. Partially reversible perfusion defect in post infarct
situation- in territory of revascularization indicates
An important method to determine ischemic burden re-stenosis.
is to perform myocardial perfusion imaging.
3. Persistent perfusion defect in new territory- indi-
The procedure involves administration of radio-tracer cates peri-procedural injury /or new stenosis.
compound at rest followed by imaging using Gamma
Camera to look at the perfusion. In normal individu- 4. Reversible perfusion defect in revascularised terri-
als, there is homogeneous distribution of radiotracer tory indicates –restenosis.
in all the segments of heart. The procedure is repeat-
ed with exercise test (Treadmill test/ Pharmacolog- 5. Persistent perfusion defect in revascularised
ic intervention using adenosine or dobutamine) an territory in absence of prerevascularisation infarc-
is expected to remain uniform in all the segments tion- indicates restenosis or peri-proceduration injury
as there is uniform vasodilatation of coronaries in
response to exercise to meet with high myocardial
demand.

Cardio Diabetes Medicine

332 Post Revascularisation Status - MyocardialPerfusion Imaging

<<< Post stress myocardial per-
fusion image-
Vertical long axis view: showing
moderate perfusion defect in in-
ferior myocardium.
<<<< Images at rest- : please
note partial improvement in per-
fusion of inferior wall

Thus myocardial perfusion helps:

1. To understand effort tolerance of the patient post
revascularization.
2. To determine left ventricular function at rest and in
post exercise period.
3. To objectively identify physiologic perfusion status
of myocardium at rest and in post exercise period.
4. To identify new territory of ischemia.

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Cardio Diabetes Medicine 2017 333

Role of Nuclear Imaging in The Evaluvation
of NonCoronary Artery Disease

Dr. Deepanjan Mitra
Dr. Anirban Mukherjee

AMRI Institute of Nuclear Medicine & PET CT,
AMRI Hospitals, Dhakuria, Kolkata

Abstract: ularity in this field especially in relation to assessment
of cardiac viability and cardiac infection/ inflamma-
Nuclear cardiology involves non-invasive assessment tion. Cardiac autonomic imaging using 123-iodine
of cardiac perfusion and function using different ra- meta-iodo-benzyl-guanidine (MIBG) and cardiac mo-
dionuclides. Apart from its common applications in lecular imaging using different radionuclides are also
the assessment of coronary artery disease, the mo- performed routinely in different clinical settings too.
dality has useful applications in non coronary artery
disease patients as well, particularly in the settings of However, most of the radionuclide studies in nuclear
non-ischemic cardiomyopathy and cardiac infection cardiology are applied in patients with coronary ar-
inflammation. Gated myocardial perfusion SPECT tery disease. GMPS is sensitive method in detecting
(GMPS) helps in differentiating ischemic cardiomyop- stress induced ischemia and also provides valuable
athy from non-ischemic cardiomyopathy. Equilibrium information regarding the viability of the myocardi-
radionuclide angiography (ERNA) helps to accurately um. However recently, with advent of different RPs,
evaluate left ventricular ejection fraction (LVEF) and nuclear imaging studies are also performed in set-
thereby determine the treatment modality in heart tings of non-coronary artery disease. In this chap-
failure patients. ERNA has been extensively used to ter, we will briefly discus the indications of different
monitor chemotherapy induced caardiotoxicity too. type sof nuclear cardiology studies in patients with
Phase analysis of ERNA and GMPS are helpful in pre- non-coronary artery disease.
dicting response to Cardiac resynchronisation ther-
apy (CRT). Cardiac autonomic innervations imaging Radionuclide imaging in non-ischemic heart
with 123-Iodine MIBG is helpful in risk stratification failure (HF)
and prognostication in patients with heart failure (HF).
FDG PET-CT has been used for myocardial infection The structural and functional abnormalities of the
and inflammation imaging. Nuclear cardiology thus myocardium in cardiomyopathy can be assessed
provides valuable therapeutic and prognostic infor- by various radionuclide imaging techniques. Radio-
mation in patients with non-coronary artery disease. nuclide imaging addresses several important clinical
questions in HF such as identifying etiology of HF
Introduction: and risk stratification. Newer approaches such as
autonomic innervation imaging, phase analysis for
Nuclear cardiology provides non-invasive assess- synchrony assessment and other molecular imaging
ment of cardiac perfusion, cardiac function and car- techniques continue to expand the applications of
diac infection/ inflammation by use of radionuclides radionuclide imaging in HF.
/ radiopharmaceuticals (RP). Gated myocardial per-
fusion SPECT (GMPS) and equilibrium radionuclide Establishing the etiology:
angiography
Most common etiology of HF is ischemic cardiac dis-
(ERNA) are two most commonly performed studies ease. Thus, it is important to rule out ischemic etiol-
in nuclear cardiology. However with introduction of ogy as a cause of HF. Myocardial perfusion studies
Positron Emission Tomography (PET), Fluorodeoxy- using 201-Thallium, 99m-Techniteum Sestamibi and
glucose (FDG) PET-CT also significantly gaining pop- 99m-Techniteum Tetrofosmin are most commonly

Cardio Diabetes Medicine

334 Role of Nuclear Imaging in The Evaluvation of Non Coronary
Artery Disease

performed to differentiate ischemic cardiomyopathy Frais et al. demonstrated utility of phase
from non-ischemic cardiomyopathy. Absence of per- analysis of gated ERNA in assessment of
fusion defect in stress and rest studies in a patient cardiac mechanical dyssynchrony [2]. The
with cardiomyopathy reliably ruled out possibilities of phase image analysis is based on the first
coronary artery disease as a cause of heart failure. Fourier harmonic fit of the blood pool time
However false negative results may happen in a case vs. radioactive curve to measure the magni-
of balanced ischemia where presence of triple vessel tude and sequence of ventricular contraction
disease mask the difference between perfusion of in each pixel of the image. A phase angle is
different segments and falsely considered as normal assigned between 0º-360º depending on the
studies. However careful evaluation of studies will relative time delay from the R-wave to the
reveal presence of transient ischemic dilatation and start of the cardiac cycle for each pixel. A
stress induced dysfunction in these cases. With ad- phase histogram is constructed correspond-
vent of PET perfusion radiotracer such as 13N-Ammo- ing to the sequence of ventricular contration
nia and 82- Rubidium this problem can be completely
solved since PET tracers give actual assessment of during cardiac cycle. Mean & Standard devi-
myocardial blood flow (coronary flow reserve) to in- ation (SD) of phase histogram is calculated
dividual segments. for each ventricle separately. Intraventricular
dyssynchrony is measured by Standard de-
Determining the therapeutic options viation of the mean phase angle (SD mPA)
for left ventricle (LV) & right ventricle (RV)
The therapeutic decision for patients with cardiomy- and interventricular dyssynchrony (IVD) is
opathy is crucial. The determination of left venricu- calculated as the difference between LV
lar ejection fraction (LVEF) to its exact value is im- and RV mean phase angles (LV-RVmPA), in
portant for decision regarding performing a surgical milliseconds (ms) and/or degree (°). Mukher-
procedure or managing the patients conservatively. jee et al. in their study of 32 patients with
ERNA, commonly known as MUGA study (Multigated non-ischemic cardiomyopathy noted that
acquisition) being the most reliable and reproducible both intra left ventricular dyssynchrony
methodology to determine the LVEF with minimal in- (ILVD) and IVD were significantly larger in
ter-observer variation, is the method of choice. Due responders vs. non responders. Reciever op-
to its reliability and repeatability it is also performed erating curve (ROC) curve analysis showed
frequently to assess LVEF during follow up. an optimal sensitivity of 95% and specific-
ity of 80% at cut-off value of 30° for ILVD
Identifying candidates suitable for device therapy & an optimal sensitivity of 81% & specificity
of 80% at cut-off value of 23˚ for IVD for
Implantable cardiac defibrillator (ICD) and cardiac re- prediction of response to CRT. However, on
synchronization therapy (CRT) are exciting treatment multivariate analysis, ILVD was found to be
options for patients with drug refractory HF [1]. How- most important independent predictor for
ever despite selecting the patient according the con- response to CRT [3].
ventional criteria, approximately one third of patients
who receive CRT will not have an improvement in LV Quantitative softwares for assessment of
function or symptoms and are called nonresponders. cardiac dyssynchrony on GMPS are com-
It has been suggested that ‘lack of a correctable form mercially available providing objective pa-
of mechanical dyssynchrony’ may be the prime rea- rameters for assessment of intraventricular
son behind the lack of response to CRT. Therefore, dyssynchrony [4]. The two parameters com-
assessment of cardiac mechanical dyssynchrony has monly used to assess cardiac dyssynchro-
gained considerable attention in recent years with ny on GMPS are Phase Standard Deviation
the aim to distinguish CRT responders from non-re-
sponders with a high degree of accuracy.

In recent years, many studies have been published
demonstrating role of nuclear imaging techniques in
predicting response to CRT. Most of these studies
are performed using ERNA and GMPS. Limited stud-
ies have also demonstrated the role of GBPS, gated
myocardial PET and myocardial autonomic imaging
in prediction of response to CRT.

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Cardio Diabetes Medicine 2017 335

(PSD) and Phase Histogram Bandwidth al flow reserve estimation have been found to have
(PHB). Mukherjee et al. in a study of non good prognostic value. Normal perfusion on SPECT
ischemic dilated cardiomyopathy patients or myocardial flow reserve on PET predicts an excel-
noted that responders had significantly lent prognosis in the intermediate term (2–5 years).
higher dyssynchrony indices of PSD (64 ±
17° vs 39 ± 13°; P<.01) and PHB (215 ± 64° vs Prognosis and risk stratification in heart
110 ± 44°; P<.01) compared to nonrespond- failure:
ers. ROC curve analysis demonstrated that
the maximum accuracy for prediction of CRT Patients with HF show increased activation of the
response was obtained with values of 128° sympathetic nervous system, reflected by an increase
for PHB and 43° for PSD (86% sensitivity and in plasma norepinephrine levels. In addition, neuronal
80% specificity for both parameters) uptake of norepinephrine is impaired in the failing
myocardium. Both the enhanced release of norepi-
(Figure 1) [5] nephrine and changes in its cardiac neuronal uptake
may be responsible for the observed downregulation
of adrenoreceptors in patients with HF [6]. Myocar-
dial innervation imaging with I-123 meta-iodo-benzyl-
guanidine (MIBG) scintigraphy provides a noninvasive
tool for the investigation of cardiac sympathetic in-
nervation. Increased norepinephrine turnover and
pre-synaptic norepinephrine deficits can be identified
as an increased MIBG washout rate (WR) from the
heart and decreased MIBG activity quantified as the
heart-to mediastinum (H/M) ratio. While the early and
delayed H/M ratios and the wash rate are thought
to reflect specific aspects of the MIBG uptake, stor-
age and release mechanisms, the delayed H/M ra-
tio has been found to be the strongest predictor of
HF prognosis in clinical studies. ADMIRE-HF study
revealed that patients with delayed H/M ratio > 1.6
had significantly better prognosis when compared
with patients with H/M ratio < 1.6 [7]. Assessment
of cardiac dyssynchrony has also been used in risk
stratification and prognostication of non-ischemic
cardiomyopathy patients [8].

Fig. 1 revealed Patient showing significant improve- Molecular imaging of HF
ment to CRT. PRE CRT MPI revealed Phase SD-52.22˚,
Histogram Bandwidth-181˚ [ Normal value-Phase SD- Molecular mechanisms of HF are operative at the
14.2± 5.1˚ (M), 11.8± 5.2˚ (F), Histogram Bandwidth -38.7± preclinical stage and imaging these mechanisms
11.8˚ (M) ,30.6± 9.6˚ (F) ]. Post CRT MPI showed signif- may lead to understanding of HF pathophysiology,
icant improvement with Phase SD-15.12˚, Histogram and starting early therapy to halt disease progres-
Bandwidth-48˚. sion. Imaging cellular mechanisms such as apoptosis
(annexin-V) and the renin angiotensin system (F-18
Follow-Up after Cardiac Transplantation captopril, F-18 lisinopril), myocardial sympathetic in-
nervation (I-123 MIBG, C-11 agents, and F-18 LMI 1195),
The role of myocardial perfusion imaging for post and myocardial metabolism (C-11 palmitate, I-123
transplant follow-up has been evaluated. Both Single BMIPP, F-18 FDG) can help to identify specific pro-
perfusion Emission computed Tomography (SPECT) cesses that may predominate in individual patients
perfusion imaging and PET perfusion with myocardi- or patient groups, and explain the heterogeneity in
response to therapy [9].

Monitoring cardiotoxicity

The guidelines for using ERNA in monitoring patients
receiving doxorubicin originally were proposed by

Cardio Diabetes Medicine

336 Role of Nuclear Imaging in The Evaluvation of Non Coronary
Artery Disease

Schwartz and co-workers [10] and have been adopt- potential to improve the early detection of myocardial
ed widely. These guidelines indicate a baseline LVEF inflammation, enable quantification of disease activi-
evaluation before beginning chemotherapy or before ty, guide therapeutic interventions, and monitor treat-
100 mg/m2 doxorubicin administration. Further serial ment success. Leukocyte scintigraphy is highly spe-
follow-up studies are based on the patient cardiac cific for infection because granulocytes are recruited
function, risk factors, and doxorubicin dose. If the to the site of infection. Whereas general utility has
baseline calculated LVEF is ≤ 30%, doxorubicin should been compromised by limited sensitivity, the imple-
not be chosen as an agent for therapy; if LVEF is mentation of single photon emission computed to-
from >30% to < 50%, follow-up ERNA should be ob- mography (SPECT) imaging has increased diagnostic
tained before each dose and doxorubicin therapy dis- performance and opened new possibilities in settings
continued when LVEF declines ≥ to 10% and/or LVEF in which high specificity is needed, e.g., in endocardi-
is ≤ 30%; if LVEF is ≥50%, ERNA should be obtained at tis imaging. Since increased glucose metabolism due
dose of 250-300 mg/m2, 400-450 mg/m2 (at 400 to overexpression of glucose transporters and over-
mg/m2 in patient with risk factors), and before each production of glycolytic enzymes in inflammatory
higher doses after. Doxorubicin should be discontin- cells considered as a hallmark of inflammation FDG
ued if the LVEF decreases to ≥ 10% to a level of ≤ 50%. PET-CT is the standard of reference for molecular im-
A review article by Mitra et al. describes various utility aging of myocardial inflammation. Indications include
of MUGA stuy in great details [11] endocarditis, myocarditis, or sarcoidosis but as well
the detection of inflammatory changes after acute
(Figure 2) myocardial infarction (AMI). However, specificity of
FDG is hampered by physiological glucose uptake
of the myocardium whose suppression requires dedi-
cated patient preparation. This is usually done by high
fat low carbohydrate diet for 3 days followed by 12
hour of fasting. Another method of suppressing FDG
uptake is using intravenous heparin before the scan.
In order to overcome limitations of FDG, a number of
promising alternatives have recently been introduced
including imaging of somatostatin receptors which
are overexpressed on the cell surface of activated
macrophages. Furthermore, C-X-C motif chemokine
receptor CXCR4, which is also overexpressed by leu-
kocytes, plays a role in stem cell trafficking [12].

Fig. 2 ERNA study showing significantly low LVEF Infective endocarditis:
with broad phased histogram suggesting dysynchro-
nous LV myocardium Early diagnosis of infective endocarditis (IE) remains
challenging. Combining FDG-PET/CT with the mod-
Cardiac Infection/ inflammation imaging: ified Duke Criteria resulted in increased sensitivity
without any change in specificity. Reliability of FDG
Cardiac inflammation can be caused by many differ- PET-CT in native valve endocarditis is limited, but its
ent conditions such as endocarditis, infection of an accuracy in diagnosis of prosthetic valve endocarditis
intracardiac device, myocarditis, cardiac sarcoidosis, and systemic complications of IE is high. Therefore
and amyloidosis. in 2015 FDG-PET/CT was included in the guidelines
of the European Society of Cardiology as a major
Compared with conventional methods, new non-in- criterion for diagnosing IE in patients with prosthetic
vasive approaches targeting inflammation have the valves. Incorporation of CT angiography into the PET/
CT scan further improves its sensitivity.. However,
specificity of the method may be limited due to arti-
facts from metal implants or due to the non-specific
biologic tracer signal. As a more specific alternative
to FDG-PET/CT, the ESC guidelines included SPECT/
CT imaging with radiolabeled autologous white blood
cells (WBC). Whereas this technique has proven its
value in detection of endocarditis , general applica-

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Cardio Diabetes Medicine 2017 337

tion was compromised by limited sensitivity due to vestigated. In a rat model of autoimmune myocardi-
a weak signal from the valvular target region and tis, feasibility of [11C]-methionine-PET imaging for the
difficult localization of inflammatory foci. The speci- detection of cardiac inflammation could recently be
ficity of leukocyte scintigraphy with SPECT/CT could demonstrated. Methionine accumulation co-localized
be particularly useful when diagnostic uncertainty with histologically confirmed cardiac inflammatory le-
remains after echocardiography and FDGPET/ CT, sions and [18F]-FDG-uptake, indicating that [11C]-me-
especially in patients who have had cardiac surgery thionine-PET might represent a promising imaging
within the past 4 weeks. agent for the noninvasive diagnosis of myocarditis.
Another new approach needing further evaluation in-
Fig 3. cludes targeting of somatostatin receptor 2 and has
yielded encouraging results in a clinical pilot study.

Pericarditis:

The use of FDG-PET/CT in pericarditis is generally
complementary and demonstrates its ability to detect
inflammatory tissue even in the absence of obvious
anatomical changes. Non-infectious and inflamma-
tory pericarditis presents with a mild to moderate
FDG-uptake within the pericardium, with either a dif-
fuse or focal on diffuse pattern of uptake.

Fig. 3 A 40 year old man with history of road traf- Cardiac sarcoidosis:
fic accident 4 months back. He had intertrochanteric
fracture of left femur which was fixed internally. Sub- PET/CT using FDG is by far the most commonly
sequently he had pain at the operative site without used nuclear medicine imaging technique and has
any swelling or discharge. He came for a PET scan mostly replaced [67Ga]-scintigraphy for assessment
for pyrexia of unknown origin for last two months. of cardiac sarcoidosis (CS). In comparison to Cardiac
PET CT showed a focal hypermetabolism in endocar- Magnetic Resonance (CMR), advantages of FDG-PET
dium that was subsequently found to be an infected include the biologic nature of the imaging signal, the
vegetations. potential to identify cardiac and extra-cardiac sar-
coidosis involvement, and the feasibility of imaging
Cardiac implant infection: patients with electrical devices or impaired kidney
function. Typically, CS manifests as a patchy, focal
FDG-PET/CT and leukocyte scintigraphy with SPECT/ uptake pattern. FDG-PET/CT has been demonstrated
CT have proven value for diagnosis of ICD- or pace- to reliably detect active cardiac and extracardiac sar-
maker-related infections. FDG-PET/CT has been coidosis. FDG-PET is thereby often combined with ra-
shown to be especially useful for diagnosis of pocket dionuclide perfusion imaging and electrocardiograph-
infection, but is less reliable for diagnosis of lead in- ic gating in order to rule out coronary artery disease
fection or device related infective endocarditis. or identify resting perfusion defects suggestive of
inflammation-induced tissue damage. Additionally,
Myocarditis: FDG-PET/CT in combination with perfusion imaging
has proven its value to determine the prognosis of
FDG-PET/CT after adequate patient preparation can CS patients, guiding endomyocardial biopsy and in
visualize acute myocardial inflammation to suggest predicting response to and monitoring therapy. Fig 4
active myocarditis. PET imaging may help to differ-
entiate between active and chronic disease. In order Cardiac amyloidosis:
to overcome limited specificity of FDG, novel PET
tracers for imaging of myocarditis are currently in- Little data available have demonstrated a rather lim-
ited role for FDG PET in imaging of CA. To date, the
most promising alternatives include more amyloid
specific tracers like 11C-labeled Pittsburgh B (PiB)
compound as well as 18F-labeled compounds such
as Florbetapir and Florbetaben.

Cardio Diabetes Medicine

338 Role of Nuclear Imaging in The Evaluvation of Non Coronary
Artery Disease

Conclusion 7. Jacobson AF, Senior R, Cerqueira MD, et al. Myocardial iodine- 123 me-
ta-iodobenzylguanidine imaging and cardiac events in heart failure. Re-
Nuclear imaging in patients with non-coronary ar- sults of the prospective ADMIRE-HF (AdreView myocardial imaging for risk
tery disease plays a important role in diagnosis of evaluation in heart failure) study. J Am Coll Cardiol. 2010;55:2212–21.
different disease, predicting prognosis in patients
with heart failure and guiding therapeutic options to 8. Goldberg AS, Alraies MC, Cerqueira MD, et al. Prognostic value of
the cardiologists. With the advent of new radiotracer left ventricular mechanical dyssynchrony by phase analysis in patients
in this field role of nuclear imaging in patients with with non-ischemic cardiomyopathy with ejection fraction 35-50% and
non-coronary artery disease will further progress. QRS<150 ms. J Nucl Cardiol 2014;21:57-66.

Important points: 9. Harinstein ME, Soman P. Radionuclide Imaging Applications in Cardiomy-
opathies and Heart Failure. Curr Cardiol Rep. 2016;18(3):23.
Gated myocardial perfusion SPECT (GMPS) helps
in differentiating ischemic cardiomyopathy from 10. Schwartz RG, McKenzie WB, Alexander J, et al: Congestive heart failure
non-ischemic cardiomyopathy. and left ventricular dysfunction complicating doxorubicin therapy seven-
year experience using serial radionuclide angiocardiography. Am JMed
Equilibrium radionuclide angiography (ERNA) helps 1987;82:1109-18.
to accurately evaluate left ventricular ejection fraction
(LVEF) and thereby determine the treatment modality 11. Mitra D, Basu S. Equilibrium radionuclide angiocardiography: Its usefulness
in heart failure patients. in current practice and potential future applications. World J Radiol 2012;
4 (10): 421-30
Phase analysis of ERNA and GMPS are helpful in
predicting response to Cardiac resynchronisation 12. Kircher M, Lapa C. Novel Noninvasive Nuclear Medicine Imaging Techniques
therapy (CRT).
for Cardiac Inflammation. Curr Cardiovasc Imaging Rep. 2017;10(2):6.
Cardiac autonomic innervations imaging with 123-Io-
dine MIBG is helpful in risk stratification and prog-
nostication in patients with heart failure.

ERNA has been extensively used to monitor chemo-
therapy induced caardiotoxicity.

FDG PET-CT has been used extensively for myocar-
dial infection and inflammation imaging.

References

1. YancyCW, JessupM, Bozkurt B, et al. 2013 ACCF/AHA guideline for the
management of heart failure: a report of the American college of cardiology
foundation/american heart association task force on practice guidelines.
Circulation. 2013;128:e240–327.

2. Frais M, Botvinick E, Shosa D, et al. Phase image characterization of
localized and generalized left ventricular contraction abnormalities. J Am
Coll Cardiol. 1984; 4:987–98.

3. Mukherjee A, Patel CD, Naik N,.et al. Quantitative assessment of cardiac
mechanical dyssynchrony and prediction of response to cardiac resynchro-
nization therapy in patients with non-ischaemic dilated cardiomyopathy
using equilibrium radionuclide angiography. Europace. 2016; 18:851-7.

4. Chen J, Garcia EV, Folks RD, et al. Onset of left ventricular mechanical
contraction as determined by phase analysis of ECG gated myocardial
perfusion SPECT imaging: Development of a SPECT myocardial perfusion
imaging diagnostic tool for assessment of cardiac mechanical dyssynchrony.
J Nucl Cardiol 2005; 12:687-95.

5. Mukherjee A, Patel CD, Naik N, et al. Quantitative assessment of cardiac
mechanical dyssynchrony and prediction of response to cardiac resynchro-
nization therapy in patients with nonischaemic dilated cardiomyopathy
using gated myocardial perfusion SPECT. Nucl Med Commun. 2015;
36:494-501.

6. Ungerer M, Bohm M, Elce JS, Erdmann E, Lohse MJ. Altered expression
of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the
failing human heart. Circulation. 1993;87:454–63.

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Cardio Diabetes Medicine 2017 339

Evaluvation of Cardiac Syncope And ECG
Markers of Sudden Cardiac Arrest.

Dr. Ameya Udyavar, Dr. Vinayaga Pandian,

MD(Medicine),DM,DNB (Cardiology), MD (Medicine), DNB (Cardiology),
Consultant Cardiac Electrophysiologist. Consultant Cardiologist.

Affiliation: P. D. Hinduja National Hospital,
Veer Savarkar Marg,Mahim, Mumbai 400016.

ABSTRACT Causes of Syncope:

Syncope is a common symptom presenting Causes of syncope are broadly classified as:
in emergency departments. The common causes of
syncope are vasovagal syncope, orthostatic hypo- Neurally Mediated: vasovagal syncope, situational
tension and cardiac causes. Cardiac causes tend to syncope.
be arrhythmic like bradycardias or tachycardias and
structural disorders like aortic stenosis and hyper- Orthostatic Induced: autonomic nervous system fail-
trophic cardiomyopathy. Its important to identify pa- ure (primary/secondary), drug induced.
tients with cardiac syncope as they are associated
with higher mortality. A detailed history, a meticulous Cardiac Arrythmia: tachyarrythmia, bradyarrythmia
physical examination and a precise interpretation of and channelopathies.
the ECG is important to identify cardiac etiology of
syncope. Structural cardio-pulmonary diseases: severe aortic
stenosis, hypertrophic obstructive cardiomyopathy
Evaluation of Cardiac Syncope and ECG markers of (HOCM), acute large pulmonary embolism, myocar-
Sudden Cardiac Arrest. dial infarction, severe pulmonary hypertension, aortic
dissection.
Definition of Syncope:
Others like volume depletion, anemia, metabolic
Syncope is defined as transient loss of conscious- causes like dyselectrolytemia, acidosis or alkalosis.
nesss and postural tone due to transient reduced
cerebral hypoperfusion. It is Common cause of syncope in diabetics are due to
autonomic nervous dysfunction causing othostatic
characterised by rapid onset, short duration and hypotension or cardiac causes (7, 8). Cardiac causes
spontaneous recovery (1, 2). include arrhythmias, coronary artery disease or struc-
tural heart disase.
Presyncopal symptoms like faintness, light headed-
ness precede syncope and may increase in severity Risk stratification
until loss of consciousness occurs, or they may re-
solve prior to loss of consciousness if the cerebral Patients suffering from syncope should be risk-strat-
ischemia is corrected. ified as per the presenting complaints/ history, phys-
ical examination and ECG features. This is extremely
Prevalence of Syncope: important as patients with cardiac syncope have a
higher chance of mortality in the mid and long term.
Syncope causes 1-6% of hospital admissions(3) and 1%
of emergency room visits per year (4, 5). Ten percent Risk stratification as per History:
of falls in the elderly are due to syncope. Syncope
affects the quality of life similar to any other chronic Youger patients tend to have syncope due to benign
diseases causing anxiety, depression, restricted out- causes like vasovagal syncope while elderly patients
door activities, change of employment etc. (6). tend to have cardiac/organic causes. Longer dura-
tion of syncope suggests that the underlying cause
is likely to be benign. Syncope which occurs most-

Cardio Diabetes Medicine

340 Evaluvation of Cardiac Syncope And ECG Markers of
Sudden Cardiac Arrest.

ly in standing positions or after change of posture Fig 1: Loss of R and deep Q waves.
suggest vasovagal etiology. Similarly situations like
micturition cough/exercise triggering syncope sug- 2. Small voltage QRS complex indicate lack of elec-
gest vasovagal etiology. Palpitations preceding syn- trically viable tissue and splintered QRS complexes
cope or syncope post exercise termination suggest indicate a patchy scar. Small voltage ECG may be
an arrhythmic cause. Syncope in lying down position suggestive of disorders like restrictive cardiomyopa-
mostly suggests arrhythmic/cardiac cause. thy and amyloidosis.

High risk features in history are:

Syncope post exercise or in supine position.

Palpitations at time of syncope

Family history of sudden cardiac arrest (SCA)

History of structural heart disease or coronary artery
disease (CAD)

Past history of angioplasty or bypass surgery.

Risk stratification on physical examination: Fig 2: Splintered QRS with low voltage.

High risk features suggesting cardiac etiology on 3. Severe LV hypertrophy is suggestive of hypertro-
physical examination are: phic heart disease.

Heart rate less than 60 bpm or more than 150 bpm
suggesting arrhythmic cause.

Irregular heart rate suggest atrial fibrillation with vary-
ing R-R interval.

Low blood pressure may suggest tachycardia with
fast rates.

Postural drop of BP suggests orthostatic intolerance.

Chest examination may suggest cardiomegaly.

Ejection systolic murmur is suggestive of aortic ste-
nosis/ HOCM.

S3 on examination may suggest severe LV dysfunc-
tion.

Risk stratification by ECG: Fig 3: LVH by voltage criteria: S wave in V2 + R wave
in V5 > 35 mm
Though patients of syncope may have normal ECGs,
it is important to look for subtle changes which may 4. Increased duration of QRS complex is a marker
suggest arrhythmic problem or structural heart dis- for delayed intra ventricular conduction and if more
ease. ECG changes would give a clue to cardiac eti- than 150 ms is an independent predictor of VT/VF.
ology of syncope (2).
5. ST segment and T wave changes: Persistent ST
A. ECG markers which may suggest elevation indicates aneurysm of LV or ongoing isch-
structural heart disease: emia. ST depression and/or bifid or deeply inverted
T waves suggests ischemia of myocardium. Spade
1. Loss of R waves and presence of Q wave or QS
pattern suggest a transmural scar, evolved infarct
which are substrate for arrhythmias.

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Cardio Diabetes Medicine 2017 341

shaped deep T wave inversions in anterior and lateral
leads suggest HOCM.

Fig 6: Non sustained ventricular tachycardia.

Fig 4: Persistent ST elevation in apical LV aneurysm.
Fig 7: Atrial fibrillation with fast ventricular rate.

Fig 5: Deep T wave inversions s/o HCM.

B. ECG markers suggestive of arrhythmic Fig 8: Tachy-brady syndrome with underlying sick
cause: sinus disease.

Bradyarrythmias: Sick sinus disease and advanced C. ECG markers of arrhythmic substrate:S
AV block are the common causes for syncope. Uni-
fascicular blocks like RBBB and LBBB or isolated Pre-excitation on baseline ECG during sinus rhythm:
IVCD are markers of future arrhythmias. In order of short PR interval and delta wave suggest pre excitation
severity for causing syncope are Trifascicular block > over an accessory pathway. These patients may have
Bifascicular block >Unifascicular block (RBBB/LBBB) atrial fibrillation with fast ventricular response and/or
(9). Prolonged QRS duration with LBBB has been as- an orthodromic/antidromic atrio-ventricular reentrant
sociated with increased mortality. tachycardia, which may cause syncope.

Tachyarrythmias: Atrial fibrillation/ atrial flutter with QT interval: prolonged QTc more than 440ms is a
fast ventricular rate, Ventricular tachycardias ( Id- harbinger for torsades which could be either drug
iopathic and Ischemic) may be again markers of induced or genetic due to channelopathy.
structural heart disease and be directly reponsible
for syncope. Epsilon wave in the right sided leads (V1) with or
without RBBB suggest arrythmogenic right ventricle
dysplasia.

Brugada pattern (ST elevation in leads V1, V2) may
suggest genetic abnormality. Type 2 Brugada with

Cardio Diabetes Medicine

342 Evaluvation of Cardiac Syncope And ECG Markers of
Sudden Cardiac Arrest.

saddle shaped ST elevation in V1-2 also may be seen 2. Shen WK, Sheldon RS, Benditt DG, Cohen MI, Forman DE, Goldberger ZD,
on the ECG. et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management
of Patients with Syncope: A Report of the American College of Cardiology/
Fig 9: Type A WPW syndrome with positive R in V1 American Heart Association Task Force on Clinical Practice Guidelines, and
with right precordial T wave inversions. the Heart Rhythm Society. Heart Rhythm. 2017.

Fig 10: ECG patterns of different types of Brugada 3. Kapoor WN. Evaluation and outcome of patients with syncope. Medicine
syndromes. (Baltimore). 1990;69(3):160-75.

D. Newer markers for risk stratification: 4. Brignole M, Disertori M, Menozzi C, Raviele A, Alboni P, Pitzalis MV, et
al. Management of syncope referred urgently to general hospitals with and
Non invasive ecg markers such as T wave alternans without syncope units. Europace. 2003;5(3):293-8.
(9, 10), heart rate variability(9) and late potentials (de-
tected by SAECG) (11) have been found to have higher 5. Blanc JJ. [The best of 2001. Heart stimulation]. Arch Mal Coeur Vaiss.
incidence of sudden cardiac arrests in some studies. 2002;95 Spec No 1(5 Spec 1):29-32.
However, they have not found of much utility in clin-
ical practise(9). 6. Linzer M, Prystowsky EN, Divine GW, Matchar DB, Samsa G, Harrell F,
Jr., et al. Predicting the outcomes of electrophysiologic studies of patients
with unexplained syncope: preliminary validation of a derived model. J Gen
Intern Med. 1991;6(2):113-20.

7. Jha S, Nag D. Sympathetic skin response and autonomic dysfunction in
diabetes. Indian J Physiol Pharmacol. 1995;39(2):149-53.

8. Dandona P, James IM, Woollard ML, Newbury P, Beckett AG. Insta-
bility of cerebral blood-flow in insulin-dependent diabetics. Lancet.
1979;2(8154):1203-5.

9. Camm AJ, Pratt CM, Schwartz PJ, Al-Khalidi HR, Spyt MJ, Holroyde MJ, et
al. Mortality in patients after a recent myocardial infarction: a randomized,
placebo-controlled trial of azimilide using heart rate variability for risk
stratification. Circulation. 2004;109(8):990-6.

10. Pastore JM, Laurita KR, Rosenbaum DS. Importance of spatiotemporal
heterogeneity of cellular restitution in mechanism of arrhythmogenic dis-
cordant alternans. Heart Rhythm. 2006;3(6):711-9.

11. Dinov B, Bode K, Koenig S, Oebel S, Sommer P, Bollmann A, et al. Sig-
nal-Averaged Electrocardiography as a Noninvasive Tool for Evaluating the
Outcomes After Radiofrequency Catheter Ablation of Ventricular Tachy-
cardia in Patients With Ischemic Heart Disease: Reassessment of an Old
Tool. Circ Arrhythm Electrophysiol. 2016;9(9).

Highlights:

Syncope is a benign disorder in majority of patients.

It is important to rule out cardiac/arrhthymic etiology
as these patients have higher mortality in the long
term.

A detailed history and a meticulous physical exam-
ination constitute the first step towards evaluation of
patients with syncope.

Precise interpretation of the ECG is important to iden-
tify cardiac etiology of syncope.

References:

1. Task Force for the D, Management of S, European Society of C, European
Heart Rhythm A, Heart Failure A, Heart Rhythm S, et al. Guidelines for
the diagnosis and management of syncope (version 2009). Eur Heart J.
2009;30(21):2631-71.

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Cardio Diabetes Medicine 2017 343

Myocardial Imaging Products :
Continuing Evolution For The Better

Dr. N. Ramamoorthy Dr. Meera Venkatesh

Ph.D. Chemistry
Retiree from BARC-DAE, Mumbai; Chairman,
SARCAR, AERB, Mumbai; Adjunct Faculty,
SoAHS, Manipal Univ. Mysore.

Abstract: specificity and sensitivity, was a challenge.This led
to investigating a range of products providing valu-
The role of myocardial imaging in nuclear medicine able information of different nature and there has
(NM) has been well recognized in the management been an evolution over time, both in products and
of patients of coronary artery diseases. It is reported imaging instrumentation. This article tries to briefly
that nearly 40-50% of all diagnostic imaging done capture the salient developments and the ever-con-
in NM (over 40 million studies per annum) is of the tinuing changes for the better.
myocardium (depending upon the region/country),
and thus nuclear cardiology(NC) has become an im- Myocardial perfusion markers:
portant branch of NM. The radiopharmaceuticals and
techniques evolved over time are for mapping mainly The search for a suitable radioisotope tracer for myo-
the blood flow to myocardium (using potassium ionic cardial imaging as a mimic of intra-cellular K+ (due to
analogs: 201Tl+, 13NH4+, 82Rb+, [99mTc(X)n]+), and demon- non-availability of a suitable potassium radionuclide
strating viability (trapping of fatty acid analog (123I - (RN)) with the then prevalent planar gamma camera
fatty acid) or glucose analog (18FDG)). The advent of was the starting point in the evolution of myocardial
SPECT and PET-CT has helped enhance the image perfusion imaging (MPI) agents. In mid-1970s the ad-
quality as well as quantitation capability, strength- vent of 201Tl+ tracer - mimic of K+ due to similarity of
ening the NC practices further. The dream-wish in ionic size and charge - heralded a major milestone
the continuing evolution is to develop an efficacious in the history of radiopharmaceutical and nuclear
product, which can medicine.

specifically image the atherosclerotic lesions within Thallium-201 as201TlCl (74 h half-life; Eg 135 & 167
coronary arteries, although many challenges need to keV; 69-80 keV Hg X-rays): The following features
be addressed. of 201TlCl led to its facile deployment: high myocar-
dial extraction of 201Tl+ ensuring that 3-4% of the
Preamble: administered dose of 201Tl (50-75 MBq (about 1.5-2
mCi)) being taken up by the myocardium; relative-
Myocardial imaging has been an extremely import- ly slower uptake and slower wash-out of 201Tl+from
ant contribution of nuclear medicine (NM) for the ‘compromised but viable’ myocardial tissue (ischemic
management of patients of coronary artery diseas- areas), as compared to normal myocardial cells; fast
es (CAD, IHD). The role of NM imaging,to map the blood clearance; excretion by renal system, etc. This
blood flow to the myocardium (myocardial perfusion), helped obtain stress and rest images of myocardial
as well as to demonstrate viability of myocardial seg- perfusion, with a single injection of 201TlCl and im-
ments, has been of considerable value to cardiolo- aging twice, early (injection of tracer at peak exer-
gists in planning management strategies, and/or for cise and imaging soon after) and a delayed image
subsequent follow-up. Though one of the early aims at 3-4 h p.i.). This led to the success of201Tl imaging
of diagnostic nuclear medicine imaging was to visu- in NM, despite the relatively low resolution images
alise the myocardium so as to assess the functional obtained with the planar gamma camera (GC). The
adequacy, the path of developing and deploying suit- term ‘redistribution’ was much used for information
able radiopharmaceutical products, of the required

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344 Myocardial Imaging Products : Continuing Evolution For The Better

content in the delayed image, though it was a mis- lipophilic) in planar imaging could also be avoided
nomer; the difference was due to differential wash- to a large extent by SPECT. The rest is history, with
out of the tracer between high and low blood flow nearly 40-50% of all the large volume imaging done
regions. With the advent of SPECT, there was an with 99mTc being that of myocardium. It is said that
important change for the better, superior resolution one 99mTc based imaging study is being done every
image slices of myocardial perfusion became a rou- second somewhere in the world, and thus, one myo-
tine feature, with dose of 201TlClincreased (up to 130 cardial imaging study using 99mTc is being done once
MBq (3.5 mCi)). 201Tl has been a good physiological every 2 to 2.5 seconds. Further, the ability to acquire
tracer for MPI, but is not ideal from the point of view ECG-gated images (when required), with the larger
of image quality and higher absorbed radiation dose amount of injected dose possible in the case of 99mTc
to the patients. Medical cyclotrons (MC) of 30 MeV products, render it possible for acquiring ECG-gat-
protons (of a Belgium company) became highly pop- ed-data and deriving cardiac pumping parameter (left
ular for deployment for production of 201Tl. 201Tl was ventricular ejection fraction, LVEF), in addition to MP
produced by (p,3n) reaction on enriched 203Tl target, imaging.
followed by a 2-stage processing, using automated
radiochemical processing module, and rendering reli- PET tracers - 13NH4+, 82Rb+, 18F: The fastest growing
able availability of 201TlCl for medical usefor well over imaging modality since 2001is PET-CT, and this has
two decades, and, in turn, made nuclear cardiology turned the focus on PET tracers for MPI. PET modality
a regular feature of clinical NM. has the advantage of attenuation correction leading
to superior resolution images of the ‘defective’ re-
Technetium-99m compounds: gions, as well as better quantitation feature. 82Sr-82Rb
generator, and the use of 82Rb+ (K+ analogue) for PET
The well-established merits of 99mTc (6 h half-life; Eg imaging of myocardial perfusion, has increasingly at-
140.5 keV (89%)) for high quality imaging triggered tracted global attention, particularly after the 2008-
in late 1970s and early 1980s much R&D efforts 2010 supply crisis of 99Mo-99mTc. 82Sr with a half-life
world over for developing 99mTc-based myocardial of 25 days renders generators of shelf-life of about a
agent. The approach was to design and optimise month or two. Half-life of 82Rb (75 seconds) is favour-
a moderately lipophilic, cationic complex of 99mTc, able for repeat cardiac studies, wherever warranted,
to mimic the potassium/thallous ion, and facilitate as for example, for certain need-based physiologi-
uptake by the myocardium and fast clearance from cal and/or pharmacological intervention procedures.
the blood pool. This culminated in the development The other PET tracerto cite is13NH3(10 min half-life)
and launch of Tc(I) hexakis isonitirle mono-cationic as 13NH4+ for MPI, although it is not of large use due
complex, called 99mTc-sestamibi, by a US-based com- to requirement of on-site MC.Among the many PET
pany in 1986. This was subsequently supplemented radionuclides for use in nuclear cardiology, 18F with
by another similar mono-cationic complex product, the lowest positron energy (0.635 MeV) and relatively
called 99mTc-tetrofosmin, launched by a company in long half-life of 18F, 110 min, would be the best suit-
UK. The 99mTc-based products understandably did not ed for logistics reasons and to provide high resolu-
have the same desired features as 201Tl+, and thus two tion images. Thus, 18F-flurpiridaz (structural analog of
separate injections were necessary to elicit stress pyridaben), taken up by mitochondrial binding, is a
and rest perfusion pattern in patients. Further, their product in an advanced phase of clinical evaluation
myocardial extraction efficiency is 50-60% of that of and seems set to emerge as the winner, meeting all
201Tl (compensated partly by the larger injected dose the key requirements, namely: uptake proportional to
of 99mTc, up to 740 MBq (20 mCi); 1.5-2% uptake in blood flow; convenience of 110 min half-life of 18F;
myocardium). Phasing out of 201Tl did notoccur for low positron energy enabling high resolution images;
well over the next 10-15 years, despite the advantag- relatively lower cost (cf.82Rb+,13NH4+).
es of99mTc in production logistics, patient dose and
cost; only since 2000, perceptible reduction in 201Tl Quantitation advantage with PET tracers:
use has occurred.
Over time, the role of NM myocardial imaging moved
The arrival of 99mTc based products for MPI and the beyond perfusion, responding to the importance and
entry of SPECT in NM took place more or less at role of absolute quantitation of myocardial flow, ex-
the same time. This led to MPI using 99mTc products pressed in terms of Coronary Flow Ratio (CFR - ratio
being done with SPECT, and made the image quality of the myocardial blood flow at peak hyperemia to
much superior to that obtainable with 201Tl+. The inev- resting), in management of cardiac patients with cor-
itable liver shadow with 99mTc products (being highly onary stenosis. To derive CFR values, tracers whose

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Cardio Diabetes Medicine 2017 345

uptake is directly proportional to the blood flow are 64Cu labelled VEGF analog to image VEGF receptor
required and the PET tracer,15O-water (t1/2 2.06 min) in angiogenesis), thanks to their favourable complex-
which diffuses freely across myocyte membranes, ation characteristics. This advantage can be further
with 100% extraction fraction,would be the ideal trac- harnessed for development in future of a myocardi-
er for the purpose. However, its use is limited due al perfusion PET tracer. The superior resolution PET
to practical disadvantages including the very short images, and greater quantitation capability of PET,
half-life of 2.06 minutes. Among the other myocardi- are key drivers to explorefurther in the evolution of
al perfusion PET tracers, 82Rb+ and 13NH3, are the ones myocardial imaging agents.
used despite their non-ideal myocardial extraction
fractions. 82Rb derived from a generator, has edge Markers for myocardial metabolism and
over 13NH3,and hence preferred currently for CFR es- myocardial viability
timation.
Iodine-123 labelled fatty acid analogs:
The growth in hybrid imaging using PET-CT,and avail-
ability of CT along with PET,offered an advantage for Fatty acid is the primary source of energy for myo-
estimation of another important parameter Fractional cardium, and thus radiolabelled (e.g. radioiodinated)
Flow Reserve(FFR). Recent advances in computation- analogues of fatty acid derivatives (such as ortho/
al fluid dynamics and image-based modeling have para Iodo phenyl pentadecanoic acid (IPPA)) were at-
made it possible to calculate FFR non-invasively tractive carrier molecules for myocardial imaging, e.g.
without the need for additional imaging, modifica- 123I-IPPA. Thus an early development in NM involved
tion of acquisition protocols, or administration of using iodine-123 fatty acid analogues, as tracer for
medications. This added possibility to PET-CT imag- myocardial metabolism imaging. However, this did
ing studies is yet another boost to the value-addition not live up to its full potential. 123I (13.3 h half-life; Eg
available fromnuclear cardiology. 159 keV (84%)), though an ideal agent for imaging
with gamma camera and SPECT, posed demanding
Additional PET tracers - Potential for production logistics (very highly enriched 124Xe tar-
Development: get use) as well as high cost. Furthermore, the then
mindset was that 13.3 hours half-life of 123I is too
The generator produced PET tracer 68Ga (68 min half- short for facile transportation. These factors severe-
life) is being increasingly used in NM, mostly for tu- ly impacted the exploitation of the utility of 123I-based
mour imaging. The availability of 68Ga from long shelf- myocardial agent. It is ironical that despite growth in
life 68Ge-68Ga generator is an important advantage, as the deployment of MC, and the paradigm-shift with
it obviates the need for on-site MC or dependence on respect to half-life of radionuclides in use nowadays
daily shipments. This aspect together with the amena- (e.g. the widespread distribution and use of 110 min
bility of trivalent gallium ion for complexation by a half-life 18F), interest in production and use of 123I has
variety of chelating moieties have accelerated R&D remained low. 18F labelled fatty acid analogs have
efforts for using 68Ga. Thus a welcome development been reported in the quest for a PET tracer for myo-
in the evolution of myocardial agents will be develop- cardial metabolism imaging, but with limited success.
ment of a 68Ga product for MP PET imaging in near In light of emerging use of PET radioiodine tracer124I
future. Although several synthetic cationic complex- (4.18 d), one can also consider using 124I-IPPA in future.
es of Ga(III) have been explored as 68Ga PET tracers
for MPI (e.g. gallium(III)-(bis(3-isopropoxy-2-phenolate PET tracers:
-benzylidene)-N,N’-bis(2,2-dimethyl-3-amino-propyl)
ethylenediamine),68Ga-based product with biochem- The role of nuclear medicine to directly show the ex-
ical and pharmacokinetic properties well-suited for tent of viability in the suspect segments or damaged
PET MPI, with high contrast perfusion images of the or injured myocardium has been well-recognised,
heart combined with rapid clearance from the liver,is especially after18F-2-fluoro-2-deoxy glucose (18FDG)
yet to be achieved. entered clinical NM practice. Now that medical cy-
clotrons (MC) and PET tracer like 18FDG have become
Another positron emitter with high potential for ex- commonplace items (16 MC and over 120 PET-CT now
ploitation is Copper-64, which is already being much in India), NM’s value addition to managing cardiac
investigated for tumour imaging. The 12.4 h half-life patients by demonstrating myocardial viability in an
of 64Cu makes it more attractive for production and unequivocal manner can be more increasingly put to
distribution logistics. 68Ga and 64Cu have been used clinical use. The blood flow starved lesion(s) shown
in NM with effective linker molecules to biologically on the MP images with 99mTc + SPECT, lighting up
(or biochemically) interesting carrier molecule (e.g.

Cardio Diabetes Medicine

346 Myocardial Imaging Products : Continuing Evolution For The Better

with 18FDG on PET image, would help plan, or confirm evolved well over time, with mapping the blood flow
the plan, for the subsequent interventions required to myocardium remaining the major procedure, per-
(or otherwise).18FDG, well-known for its contributions formed using potassium ionic analogs: 201Tl+, 13NH4+,
in cancer care, can be harnessed in addition for the 82Rb+, [99mTc(X)n]+.
benefit of cardiac patients. Also, many other 18F prod-
ucts are under investigation, including a few under- Myocardial viability/metabolism imaging is increas-
going clinical trials. ingly being done by the trapping of glucose analog
(18FDG), while use of fatty acid analog (123I - fatty acid)
Epilogue: has been a known sound approach since early times.

Myocardialimaging to elicit, sites of low or nil per- SPECT and PET-CT have helped enhance the image
fusion, and/or viability of the correspondingseg- quality as well as quantitation capability, strengthen-
ment(s),provides evidence-based functional informa- ing the practices further.
tion as NM’s unique support, with low radiation dose
(5-10 mSv), for the management of cardiac patients. Evolution of products/techniques continues with
The recent emergence of (multi-slice) angio-CT has researchers seeking, despite many challenges,to
already added a powerful non-invasive imaging tool achieve a productspecific for atherosclerotic lesions
(12 mSv) to the cardiologist in the investigation of in the coronary arteries.
patients of CAD; and so, what can NM and radio-
pharmaceuticals do to further advance nuclear car- Bibliography
diology? If only there would be a suitable radiotracer
for i.v. use that can lit up the interiors of the coronary 1. N. Ramamoorthy, Meera Venkatesh,Myocardial Imaging Products’ Evo-
arteries, almost in the same manner as the conven- lution: Change for the Better, inCardiac Imaging Update 2017, Jaypee
tional coronary angiography shows it in cath lab, that Brothers Medical Publishers, Delhi, 2017, pp. 80-84
would become truly a phenomenal achievement for
NM, however tough the odds are in the development 2. Vikas Veeranna and Sharmila Dorbala,Myocardial Perfusion Imaging with
of such a product, and in achieving the resolution PET, PET/CT, PET/MRI: Technical Advances and Future Applications, in
of the imaging instrumentation required. Some prog- ‘Perfusion Imaging in Clinical Practice’, Chapter 22, Wolters Kluwer (2015)
ress in terms of potential tracers for targeting arterial pp.398-411
plaques has been reported in conferences and publi-
cations (e.g. by Orbay et al. cited in Bibliography). PET 3. Oyebola O. Sogbein, Matthieu Pelletier-Galarneau, Thomas H. Schin-
imaging of atherosclerosis could be of great help to dler, LihuiWei, R. GlennWells, and Terrence D. Ruddy, Review Article:
identify the at-risk individuals earlier in the disease New SPECT and PET Radiopharmaceuticals for Imaging Cardiovascular
process, as well as to monitor responses to thera- Disease,Hindawi Publishing Corporation; BioMed Research International;
py. Of the several PET tracers studied for imaging Volume 2014, Article ID 942960
atherosclerosis, the most commonly cited is 18F-FDG,
while 11C-choline, 18F-galacto-RGD, 11C-acetate, and 11C- 4. Jamshid Maddahi and René R. S. Packard, Cardiac PET Perfusion Trac-
PK11195 have been tested clinically. The small size of ers: Current Status and Future Directions, Semin Nucl Med(2014)44:
the atherosclerotic lesions in coronary arteries in the 333–343
vicinity of circulating tracer in blood, taken along with
the respiratory and cardiac movements during the
image acquisition,pose high degree of uncertainties.
This could be better addressed by the use of the re-
cent development of PET-MR system, where MRI can
provide high spatial resolution and exquisite soft tis-
sue contrast, to complement the PET study.

Highlights

The volume of myocardial imaging in nuclear medi-
cine (NM) is reported to be 40-50% of all diagnostic
imaging (around 40 million studies per year) per-
formed across the world, depending upon the re-
gion/country.

The radiopharmaceuticals and techniques have

GCDC 2017

Cardio Diabetes Medicine 2017 347

Pitfalls in Computer ECG Interpretations

Dr.V.BALCHANDRAN

MD,MNAMS, FRCP, FACC, FCSI, FISC, Dip.Diab,
Chief Physician-Cardio-Diabetology,
Dr.Nairs Hospital, Kollam ,Kerala,

Introduction an accuracy of only 54% with a sensitivity of 72%,
a specificity of 93%, and a positive predictive value
Since the introduction of the string galvanometer by of 59.3%. The clinical impact of the ECG-C misinter-
Willem Einthoven more than a century ago, the ECG pretation was evaluated by other investigators who
has become the most commonly performed cardio- demonstrated that 19% of ECG-C had the rhythm
vascular test and an essential diagnostic tool in clini- misinterpreted as atrial fibrillation (3). Failure of the
cal cardiology. The transition from analogue to digital physician ordering the ECG to correct the inaccurate
ECGs resulted in automated computer analysis of the interpretation resulted in change in management and
ECG (ECG-C) assuming a larger role in the diagnos- initiation of inappropriate treatment, including antiar-
tic interpretation. Yet, as the ECG-C has evolved into rhytmic medications and anticoagulation, in 10% of
a necessary tool of modern medical practice, many patients. Additional unnecessary diagnostic testing
physicians remain unaware of the hazards of relying was performed based on the misinterpreted ECGs in
on these preliminary diagnostic interpretations. The 24% of patients. The ECG-C failed to identify many
ECG-C clinical use should always be with the un- at-risk family members when used as a screening
derstanding that they are preliminary interpretations tool for long QT syndrome (LQTS). The ECG-C erro-
and require reading and confirmation by qualified neously classified 6 of 23 family members known to
electrocardiographer. With an increased reliance on have LQTS as normal
these readings for point-of-care decision making,
clinicians must remain mindful of many limitations What is the reason that the most sophisticated com-
of the ECG-C. (1)  puter ECG interpreting software makes so many mis-
takes? The answer lies in the remarkable and exten-
Pitfalls in interpretations. sive capacity of the human brain to recognize visual
patterns highly complex visual pattern recognition
Multiple prior investigations on the ECG-C interpre- system of our central nervous system. The skill in
tation have demonstrated erroneous interpretation, pattern recognition would be a carefully preserved
resulting in unnecessary, potentially harmful medical component of our brains that remains one of our
treatment, and inappropriate use of medical resourc- species greatest assets. The computer that is read-
es.  A large international study compared the perfor- ing an ECG does not have pattern recognition skills
mance of 9 ECG-C programs with that of cardiologists as yet, although this may well be developed in the
in interpreting ECGs in clinically validated cases of future. Presently, computers read ECGs by making
various cardiac disorders (2). The percentage of ECGs frequent determinations of the direction, positive or
correctly classified by the ECG-C was lower than that negative, that the ECG tracing is taking. By using this
for the cardiologists. More contemporary analysis of information, the computer calculates whether a “q”
the accuracy of ECG-C similarly concluded that there wave or ST-segment elevation or depression is pres-
are frequent errors in the interpretation of the cardiac ent. This form of ECG interpretation is clearly not as
rhythm. In evaluating the ECG-C interpretation of the accurate as the process of pattern recognition built
cardiac rhythm, the ECG-C demonstrated an overall into the human central nervous system (4). Two ECGs
accuracy of 88.0%. Sinus rhythm was correctly inter-
preted in 95.0% of the ECGs with this rhythm. Howev-
er, non sinus rhythms were correctly interpreted with

Cardio Diabetes Medicine

348 Pitfalls in Computer ECG Interpretations

on the same person recorded 15 seconds apart may mendation reads: “Computer-based interpretation
have different interpretations either because of dif- of the ECG is an adjunct to the electrocardiographer,
ferent noise levels or because physiological variation and all computer-based reports require physician over
(e.g. respiratory cycle) means a diagnostic threshold reading.
has been crossed. Between the two ECGs one com-
mon error is missing small R waves resulting in a Normal ECG reported as Abnormal
wrong diagnosis of MI. Another is under and over
diagnosis of T wave Changes . (5), (6) Fig 1 and Fig 2

In interpretation of acute cardiac ischemia sensitivity
of 76% and a specificity of 88%, for acute myocardial
infarction the sensitivity was 68% and the specificity
97% and for thrombolytic therapy found a sensitivity
of 61.5% and specificity of 90%. Hence reliance on
computer interpretation would result in inappropriate
underuse of thromobolytic therapy

Benefits of computer interpretations are it is most
accurate in computing values, most accurate in cal-
culating Heart rate, Axis , intervals (PR, QRS, QT
), it is reliable in recognizing Sinus rhythm mecha-
nisms- saves time for experienced interpreter to in-
terpret large no of ECGs, it is very useful for primary
care physicians in remote areas for decision making
(7). Computer ECG is not infallible; Arrhythmias and
conduction disorders, electronic pacemakers and
Rhythm, acute myocardial infarction, high degree AV
blocks, Atrial Fibrillation, Hyperkalemia or Hypokale-
mia, Early Repolarization, WPW syndrome RBBB and
minor wave pattern change

Conclusion. Fig 3-- Abnormal ECG reported as normal ( ECG shows
Lead 1 sign of emphysema,, pseudo infarct pattern
Given the profound clinical implications of the ECG-C,
all clinicians must be mindful of potential for errone-
ous interpretation resulting in unnecessary, potential-
ly harmful medical treatment, and inappropriate use
of medical resources. The publication by Lehman
serves to remind clinicians that the appropriate use
of the ECG-C is as a supplement, but not a substi-
tute, for interpretation by an electrocardiographer. Do
not rely on computer ECG interpretations in Neonatal
ECGs, Acute Myocardial infarction decision making
for thrombolysis, Rhythm abnormalities, Conduction
disturbances, Minor R wave forms and T wave chang-
es. Computer ECGs are only synthesized rhythm and
not real time and hence when extra systoles are re-
ported but sometimes we may not see it in the trac-
ings. A recent scientific statement by a consortium of
AHA/ACC and the HRS advises to be prudent when
using computer interpretations. The official recom-

GCDC 2017

Cardio Diabetes Medicine 2017 349

Fig 4- ECG has completely missed an RBBB References.

1. Hagan AD, Alpert JS. Evaluation of computer programs for clinical elec-
trocardiography. In: Cady L, ed. Computer Techniques in Cardiology.New
York: Marcel Dekker, Inc; 1976:77-96.

2. MMilliken JA et al, Impact of an ECG computer analysis program on the
cardiologist’s interpretation, J Electrocardiol, 1983 April (62); 141-149

3. Pordy, L. Computer analysis of cardiac arrhythmias. Cardiovasc
lin. 1970;2:281–293.

4. Milliken, J.A., Wartak, J., Lywood, D.W. et al, Validity of computer
interpretation of electrocardiogram.Can Med Assoc J. 1971;104:1147–
1150.

5. Bailey, J.J., Itscoitz, S.B., Grauer, L.E. et al, A method for evaluating
computer programs for electrocardiographic interpretation. II. Mayo
Clinic program of 1968. Circulation.  1974;50:80–87

6. Bailey, J.J., Horton, M., Itscoitz, S.B. A method for evaluating comput-
er programs for electrocardiographic interpretation. III. Reproducibility
testing and the sources of program errors.Circulation. 1974;50:88–93.

7. Joe S Williams et al, Diagnostic performance of computer programs
for the interpretations of electrocardiograms. N Engl J med, 1991,
325, 1767-1773.

Fig 5 Dextrocardia is not interpreted

Fig 6 Reported as Anterior infarct but no infarct

Cardio Diabetes Medicine

350 Cardio Diabetes Medicine 2017

“Echocardiographic Evaluvation
of A Diabetic Patient”

Prof. Dr. V. Amuthan

MD DM FACC FASE FESC FCSI FIAE
Emeritus Professor of Cardiology, The Tamil Nadu Dr. MGR Medical University

Professor & HOD of Cardiology (Retired) Madurai Medical College, Madurai
Director of 3D Echocardiography, Jeyalakshmi Heart Centre, Madurai
Senior Interventional Cardiologist, Vadamalayan Hospital, Madurai

Dr. R. V.a. Ananth
MBBS, PGDCC,
Consultant Cardiologist, Jeyalakshmi Heart Centre, Madurai

Cardiac problems develop in concert with develop- (Fig1) Evaluation of a Diabetic patient by Echocardi-
ment of Diabetes1. The 2011 estimate of 360 million ography in relation to severity
people with Diabetes globally is estimated to increase
to 552 million by 20302. This epidemic proportion of
Diabetes in the context of the fact that India is the Di-
abetic capital of the world has necessitated the early
diagnosis of Cardiac problems in Diabetes. Although
the conventional two-dimensional echocardiography
and doppler studies remain the sheet anchor of di-
agnosis, early diagnosis is missed by these technol-
ogies. Three-dimensional echocardiography and the
use of speckle tracking echocardiographic analysis
of Longitudinal, Circumferential, radial strain and LV
torsional deformation analysis score over the earlier
techniques3.4.

Conventional 2D Early Middle Late Advantages/
Echo & Dopplert Disadvantages
Abnormal Longitudi- Diastolic dysfunction Systolic dysfunc-
Tissue Doppler Im- nal & Circumferential 1.↑ E/A tion Universally available
aging strain 2.↑LV Mass ↓ LV Ejection Interobserver Vari-
3.↓ Cavity size Fraction ability
3D Echo and Strain 4.↑ Deceleration Time
by Speckle tracking Quantification of
E/e’ > 14 Abnormal strain myocardial velocities
Angle dependent
Diastolic Strain abnor- Systolic Strain
malities Abnormalities Technique is available
GLS < -14 in only high-end ma-
chines and requires
3D Echo and Myocar- Higher peak and time Attenuated and delayed expertise
LV twist and untwist
dial mechanics by LV to peak twist and angle Technique is available
in only high-end ma-
Torsion Untwist angle chines and requires
expertise

GCDC 2017

“Echocardiographic Evaluvation of A Diabetic Patient” 351

Diabetic Cardiomyopathy Hypertension or Valvular heart disease7.Three-dimen-
sional Echocardiographic stress imaging adds a new
The observation of frequent association of heart dimension.
failure and Diabetes was made by Leyden et al in
18815. However, it was Rubler in 1972, who introduced Diastolic function in Diabetic
the term Diabetic Cardiomyopathy6. The minimal cri- Cardiomyopathy
teria to diagnose Diabetic Cardiomyopathy include
1. Concentric Left Ventricular Hypertrophy with Abnormal E/A and Deceleration time: Abnormal re-
LV diastolic dysfunction and Interstitial fibrosis laxation characterised by decreased E/A ratio and
2. Eccentric Dilated Cardiomyopathy with re- prolonged Deceleration time and Restrictive pattern
duced left ventricular systolic function with increased E/A ratio and decreased Deceleration
independent of Coronary Artery Disease, Systemic time are well described in early studies8

Abnormal E/e’ Ratio:

The ratio of early diastolic flow velocity of mitral inflow (E) to early diastolic mitral annular velocity (E/e′) has
been shown to be the most accurate non-invasive marker of elevated LV filling pressure9,10. In particular, echo-
cardiographic indices of elevated LV filling pressure are clearly associated with poor cardiac functional and
clinical outcome. E/e′ > 15 is the strongest predictor of cardiac death and readmission for heart failure. (Fig 2)

Mitral Flow Spectral Doppler, Tissue Doppler medial mitral annular movement and left ventricular basal and
apical rotation (negative and positive waves) during one cardiac cycle.

A.Normal subject. untwisting velocities, are both attenuated and delayed.
D.Diabetic Cardiomyopathy and reduced Ejection
Normal values for LV rotation and net twist angle in Fraction
a recent study of a large group of healthy volunteers
reported a mean value of peak LV twist angle as 7.7 LV Mass Assessment:
3.5°
Calculation of LV Mass by M Mode (cube formula)
B.Diabetes without LV hypertrophy. Note less and two-dimensional echocardiography ( Area length
prominent initial clockwise twist, higher peak or Truncated Ellipse) are cumbersome geometrical as-
twist, delayed time to peak and lower untwist- sessments that are not applicable when there is Left
ing during early diastole in the patient with di- ventricular distortion or fore shortening, Asymmetric
abetes compared with the normal subject. Left ventricular hypertrophy, Dilated cardiomyopathy
C.Advanced Diabetes and Left ventricular hypertrophy and in patients with regional wall motion abnormali-
and normal Ejection fraction. Note the relatively pre- ties12,13. The Left ventricular mass calculation is based
served LV twist mechanics, although LV twisting and on converting volume to mass using multiplication

Cardio Diabetes Medicine

352 Cardio Diabetes Medicine 2017

of volume by myocardial density of 1.05 g/mL and to identify subclinical LV dysfunction. GLS is calculat-
is normalized for the Body surface Area as LV Mass ed using a variety of proprietary software (EchoPAC,
Index. Left ventricular Hypertrophy is defined as Left GE Medical Systems, Milwaukee, Wisconsin, USA;
ventricular Mass Index of >115g/m2 and >95g/m2 for Syngo velocity vector imaging, Siemens, Mountain
women14. 3D Echocardiographic quantification of LV View, California, USA; LV analysis, TomTec GmbH,
Mass correlates better with CMR measurements15.16. Unterschlessheim, Germany). GLS is well validated
as a marker for the measurement of LV longitudinal
Evaluation of Left Atrium: deformation, which has emerged as a sensitive and
specificmarker to detect early and subtle myocardial
Left atrial size is a powerful marker of prognosis in dysfunction. In one of the recent meta-analysis, Ka-
Diabetes under a variety of clinical situations and is lam et al, have shown the independent prognostic
a strong predictor of mortality and morbidity17. Be- significance of GLS in patients with mild LV global
cause, 3D volume calculation of left atrium is devoid impairment. The prognostic value of this information
of geometrical assumptions, it correlates better with seems likely to be superior to that provided by LVEF.23
Cardiac Magnetic Resonance Imaging18. Normal Left
Atrial maximal volume and Total emptying fraction LV Torsional deformation and 3-Dimensional
have been published19. Regional assessment of left Speckle Tracking Echocardiography:
atrial function by Speckle tracking Echocardiography
has also evolved to be a novel Echocardiographic Shortening and lengthening which are the basic
technique20. functions of the myocardial fibres result in a systol-
ic twist followedby a diastolic untwisting of the left
Echocardiographic assessment of systolic ventricle due to helical orientation of the fibres.In
dysfunction LV Ejection fraction: systole, the LV apex undergoes a counterclockwise-
rotation about its longitudinal axis as viewed from
The cornerstone of the prognostication and treat- the apex.Rotation of the LV base in systole is oppo-
ment schedule for Echocardiographic evaluation of site in directioncompared to apical rotation. Thismo-
Diabetic cardiomyopathy starts with evaluation of tion has been compared with that used tosqueeze
left ventricular ejection fraction. The evidence base water out of a wet towel. The main determinant of
for modern cardiology is so heavily based on this the LV twist is the apical rotation. Three-dimension-
simple measurement that it is unlikely to disap- al speckle tracking echocardiographyhas emerged
pear.The problems in calculating EF as the ratio be- as an alternative non-invasivetechnique to assess
tween stroke volume and end-diastolic volume are LV rotation.The problems with 2D Speckle Tracking
geometry dependence, load dependence, the effect Echocardiography are the lower valuesfor apical ro-
of high and low heart rate due to heart blocks, Tachy- tation and LV twist, due to difficulties in selection of
cardias(especially Atrial Fibrillation) and insensitivity optimal imaging planes for computation,as the im-
to minor change when close to 50%21. 3D imaging is ages are acquired separately from entirely different
now available with echocardiography and its results cardiac cycles and rotation at each level peaks at a
are comparable to Cardiac MRI22. The main attraction different time in the cardiac cycle. A recent study by
and advantage of 3D imaging is to avoid geometric Muhammad Ashraf et al., to compute left ventricular
assumptions when calculations of LV volumes, and (LV) twist from 3-dimensional (3D) echocardiography
reduction of errors created by cutting a 3D structure concluded despite lower spatiotemporal resolution of
in two dimensions. The current software for 3D eval- 3D echocardiography, LV twist and torsion can be
uation of LVEF is much easier and can be performed computed accurately23LV twist is reduced in Dilated
within minutes in the setting of emergency room. The cardiomyopathy due to cardiac fibrosis resulting in
sphericity index derived from 3D echocardiography alteration of myocardial fibre orientation. Fig 2 shows
(LVEDV divided by the volume of a sphere whose di- abnormally reduced twist and torsion in a normal in-
ameter is the LV end-diastolic long axis) is an added dividual, a patient with early diabetes without LVH,
by product and is the best predictor for LV dilatation in a patient with severe LVH and finally in a patient
with diabetic cardiomyopathy and LV dysfunction. A
Strain Imaging in decision making in decreased and delayed systolic LV torsion as well as
Diabetic Cardiomyopathy depressed, delayed and disorganised LV untwisting
have been previously reported in patients with dilat-
Global Longitudinal strain (GLS): ed cardiomyopathy (DCM). Moreover, paradoxical re-
versal of LV rotation, with the base rotating counter
Global longitudinal strain (GLS) has evolved as one of clockwise and the apex clockwise, with subsequent
the most robust parameter, and this has been shown

GCDC 2017

“Echocardiographic Evaluvation of A Diabetic Patient” 353

reduction or even loss of LV twist was observed in making?European Heart Journal (2016) 37, 1196–1207
some patients with DCM.
4. Sorrentino R, Esposito R, Pezzullo E, Galderisi M: Realtime threedimen-
Case Examples: (Fig2) sional speckle tracking echocardiography: technical aspects and clinical
applicationsResearch Reports in Clinical Cardiology 2016,7: 147—158
A. Normal subject.
5. Asghar O, AlSunni A, Khavandi K, Khavandi A, Withers S, Greenstein A, et
Echo evaluation from a control nondiabetic non-hy- al. Diabetic cardiomyopathy. Clin Sci Lond Engl. 1979;2009(116):741–60.
pertensivefifty years individual. Note the normal E/A
ratio, Deceleration time, E/e’ ratio and apical counter 6. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A.
clockwise and basal clockwise rotation. Normal val- New type of cardiomyopathy associated with diabetic glomerulosclerosis.
ues for LV rotation and net twist angle in a recent Am J Cardiol. 1972;30:595–602.
study of a large group of healthy volunteers reported
a mean value of peak LV twist angle as 7.7 ± 3.5° 7. Seferović PM, Paulus WJ. Clinical diabetic cardiomyopathy: a twofaced dis-
B. EarlyDiabetes without LV hypertrophy. Note the ease with restrictive and dilated phenotypes. Eur Heart J. 2015;36:1718–
attenuation of E wave or early filling wave, prolon- 1727–1727a–c.
gation of the deceleration time and accentuation
of A wave or atrial filling velocities. There is also 8. Lang, R.M., Bierig, M., Devereux, R.B., Flachskampf, F.A., Foster, E., Pel-
alteration of E/e’ ratio. Note less prominent initial likka, P.A. et al. Recommendations for chamber quantification: a report
clockwise twist, higher peak twist, delayed time from the American Society of Echocardiography’s Guidelines and Standards
to peak and lower untwisting during early diastole Committee and the Chamber Quantification Writing Group, developed in
in this patient, compared with the normal subject. conjunction with the European Association of Echocardiography, a branch
C. Advanced Diabetes and Left ventricular hypertro- of the European Society of Cardiology. J Am SocEchocardiogr. 2005; 18:
phy and normal Ejection fraction. Note the Pseudo 1440–1463
normalization with normal E/A ratio, Deceleration
time and abnormal E/e’. Note the relatively preserved 9. Galderisi M. Diastolic dysfunction and diabetic cardiomyopathy: evaluation
LV twist mechanics, although LV twisting and un- by Doppler echocardiography. J Am Coll Cardiol 2006; 48:1548.
twisting velocities, are both attenuated and delayed.
D. Diabetic Cardiomyopathy and reduced Ejection 10. Bouchard A, Sanz N, Botvinick EH, et al. Noninvasive assessment of
Fraction: Note the abnormally increased E/A ratio, de- cardiomyopathy in normotensive diabetic patients between 20 and 50
creased deceleration time and E/e’. There is marked years old. Am J Med 1989; 87:160.
reduction in amplitude of apical counter clockwise
and basal clockwise rotation. 11. Pérez JE, McGill JB, Santiago JV, et al. Abnormal myocardial acoustic prop-
erties in diabetic patients and their correlation with the severity of disease.
Conclusion: J Am Coll Cardiol 1992; 19:1154.

Evaluation of all diabetic patients with echocardiog- 12. MenhelKinno, Alfonso H. Waller and Julius M. Gardin. Approach-
raphy for the presence of Diabetic Cardiomyopathy es-to-echocardiographic-assessment-of-left-ventricular-mass. What does
leads to detection of early and preventable changes. the echocardiography add? Expert analysis. American College of Cardi-
Thus, the treatment approaches may be changed ology 2016 Feb 3
in these conditions to include the cardio protective
drugs, for an example DPP4 inhibitors and statins. 13. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac
chamber quantification by echocardiography in adults: an update from
References the American Society of Echocardiography and the European Association
of Cardiovascular Imaging. J Am SocEchocardiogr2015;28:1-39.e14.
1. Lorenzo-Almorós A, Tuñón, M. Orejas. J, Cortés, J. EgidoM and LorenzoÓ
Diagnostic approaches for diabetic cardiomyopathy: Cardiovascular Dia- 14. Koren MJ, Devereux RB, Casale PN, et al. Relation of left ventricular
betology2017, 16: 28 mass and geometry to morbidity and mortality in uncomplicated essential
hypertension. Ann Intern Med 1991;114:345-52.
2. Lars Rydén Peter J. Grant Stefan D. Anker Christian Berne Francesco
Cosentino Nicolas Danchin Christi Deaton Javier Escaned Hans-Peter 15. Chuang ML, Beaudin RA, Riley MF, et al. Three-dimensional echocardio-
Hammes: ESC Guidelines on diabetes, pre-diabetes, and cardiovascular graphic measurement of left ventricular mass: comparison with magnetic
diseases developed in collaboration with the EASD: The Task Force on resonance imaging and two-dimensional echocardiographic determinations
diabetes, pre-diabetes, and cardiovascular diseases of the European Soci- in man. Int J Card Imaging 2000;16:347-57.
ety of Cardiology (ESC) and developed in collaboration with the European
Association for the Study of Diabetes (EASD)Eur Heart J 2013, 34 (39): 16. Mor-Avi V, Sugeng L, Weinert L, et al. Fast measurement of left ventricular
3035-3087. mass with real-time three-dimensional echocardiography: comparison with
magnetic resonance imaging. Circulation 2004;110:1814-8.
3. Otto A. Smiseth, Hans Torp, Anders Opdahl, Kristina H. Haugaa, and
StigUrheim: Myocardial strain imaging: how useful is it in clinical decision 17. Leung DY, Boyd A, Ng AA, Chi C, Thomas L. Echocardiographic evaluation
of left atrial size and function: current understanding, pathophysiologic cor-
relates, and prognostic implications. Am Heart J. 2008;156:1056–1064.
doi: 10.1016/j.ahj.2008.07.021.

18. Mor-Avi V, Yodwut C, Jenkins C, Kühl H, Nesser HJ, Marwick TH, Fran-
ke A, Weinert L, Niel J, Steringer-Mascherbauer R, Freed BH, Sugeng
L, Lang RM. Real-time 3D Echocardiographic quantification of left atrial
volume: multicenter study for validation with CMR. JACC Cardiovasc Im-
aging. 2012;5:769–777.

19. Luigi P. Badano, Marcelo H. Miglioranza, SorinaMihăilă, DilettaPeluso, Jola
Xhaxho, Martina PerazzoloMarra, UmbertoCucchini, Nicola Soriani, Sabi-
no Iliceto, DenisaMuraru, Left Atrial Volumes and Function by Three-Di-
mensional Echocardiography Reference Values, Accuracy, Reproducibility,

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and Comparison With Two-Dimensional Echocardiographic Measurements.
Circ Cardiovasc Imaging. 2016;9: e004229
20. Matteo Cameli, Matteo Lisi, Francesca Maria Righini and Sergio Mondillo:
Novel echocardiographic techniques to assess left atrial size, anatomy and
function. Cardiovascular Ultrasound 2012, 10:4
21. Thomas H Marwick. Methods used for the assessment of LV systolic func-
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curacy of echocardiographic measurements of left ventricular parameters
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Cardio Diabetes Medicine 2017 355

Biochemical Evaluation of Dyslipidemia

Dr.Devaki Nair, BSc, MSc, MBBS, FRCP, FRC (Path)

Consultant and Honorary Senior Lecturer in Clinical Biochemistry
Clinical Lead for Clinical Biochemistry -RFH and NMUH
Clinical Lead for Lipids and CVD Prevention
Director SAS Centre for Cardiovascular Biomarkers
Royal Free London NHS Foundation Trust
London

INTRODUCTION ified fatty acids (NEFAs) that is available for hepatic
uptake. Some of the NEFAs that are liberated by the
Genetic, epidemiological and histopathological stud- hydrolysis of chylomicrons releases NEFAs which are
ies have clearly established the primary role of plas- hepatically removed and used for VLDL-TG produc-
ma lipids and lipoproteins in the development of tion and secretion. Insulin resistance in impairs fatty
atherosclerotic disease. Lipid disorders, also called acid storage and raises plasma NEFAs, which are
dyslipidaemia, are abnormalities of lipoprotein me- used for VLDL production accounting for the raised
tabolism and include elevations of total cholesterol, fasting TG in diabetes as well s post prandial rise
LDL cholesterol, or triglycerides; or deficiencies of in TG. Increased hepatic lipase divers NEFA to the
HDL cholesterol. These disorders can be acquired liver making VLDL-TG.The structure, production, re-
or familial (e.g., familial hypercholesterolemia). The modeling, and catabolism of HDLs have been more
preferred screening tests for dyslipidaemia are total difficult to study than those for the apoB containing
cholesterol HDL cholesterol levels and triglyceride lipoproteins. HDLs are small and heterogeneous with
levels on non-fasting or fasting samples. There is respect to size and composition. They are involved
currently sufficient evidence of the benefit of includ- in Reverse cholesterol transport (RCT) that compris-
ing triglycerides as a part of the initial tests used to es three steps within the context of cardiovascular
screen routinely for dyslipidaemia. Abnormal screen- disease (CVD):
ing test results should be confirmed by a repeated
sample on a separate occasion, and the average of Abnormal lipid profile is common and several termi-
both results should be used for risk assessment. nologies are used to explain these abnormalities

Plasma lipids are transported by lipoproteins, which Hyperlipoproteinemia: abnormally elevated concen-
are defined by the densities at which they are iso- trations of specific lipoprotein particles in the plasma.
lated, that is, as the high-, low-, intermediate-, and
very low-density lipoproteins. (HDLs, LDLs, IDLs, Hyperlipidemia: increased plasma cholesterol and/or
and VLDLs, respectively); chylomicrons, are intesti- triglyceride
nally derived, consists of mainly dietary lipids and
small amounts of protein. HDL-C appears in two sub- Dyslipidemia:
classes, HDL2 and HDL3. Through a simple blood test,
plasma lipoprotein levels, which are among the most abnormal cholesterol (TC, LDL-C, or HDL-C) and/or
important risk factors for coronary artery disease, TG concentrations. Dyslipidaemia includes low HDL
provide clues about the aetiology of lipid disorders concentration as well as abundance of small dense
and about their most prominent pathologic associ- LDL.
ations.VLDL and chylomicrons are assembled and
secreted by hepatocytes and enterocytes in the liver Dyslipidaemia is clinically important because of the
and intestine, respectively. driven by the TG synthesis complications related to atherogenesis ie coronary
from endogenous and exogenous, pathways that is, artery disease, cerebrovascular disease and periph-
dietary, fatty acids. An important determinant of fast- eral vascular disease; however, These disorders may
ing plasma TG concentration is the plasma Nonester- manifest as pancreatitis and fatty liver disease.

Cardio Diabetes Medicine

356 Biochemical Evaluation of Dyslipidemia

Lipoprotein(a) (Lp[a]) similar to LDL and are syn- 4. C-reactive protein
thesized in the liver. Lp(a) differs from LDL by the
addition of Apo(a), a protein with a structure that is 5. Cell adhesion molecules
homologous to plasminogen. High levels of Lp(a)
are both prothrombotic and proatherogenic. Levels Special Investigations:
of Lp(a) in plasma are determined by genetic varia-
tion in the two Lp(a) alleles. While investigating dys- 1.Measurement of Apolipoproteins may be required in
lipidaemia it is essential to consider those tests that assessing vascular risk or for diagnosis of inherited
are useful for routine CVD risk assessment as well deficiencies or excesses
as additional risk factors
2.Tests are also required to rule out different types
While investigating lipid abnormalities the first step of primary hyperlipidaemias are useful in those with
is to differentiate between primary and secondary inherited hyperlipidaemia.
hyperlipidaemia and therefore the following should
be considered In Type 1 hyperlipidaemia or Familial chylomicronae-
mia syndrome (FCS)
-Tests to establish primary /secondary hyperlipidae-
mia This is an autosomal recessive condition which is
characterized by excessive circulating chylomicrons
-Tests that establish additional risk due to defective or absent LPL activity, often calcu-
lated LDL-C is not available ,when lipid profile is re-
-Lipid related quested in these subjects as the TG level is high and
the Friedewald formula for calculating LDL-C is in-
-non- lipid related accurate. High TG levels interfere with measurement
of LDL-C and other analytes like sodium concentra-
The Following investigations are required to exclude tion depending on the method used. A simple test
secondary causes involves placing the tube in which the blood sample
was centrifuged in a refrigerator, to demonstrate the
Urine dipstick test to rule out proteinuria, thereby ex- creamy layer with a clear serum layer separating it
cluding nephrotic syndrome and some other forms from the red cells and can be called a ‘fridge test’
of renal disease and is a very specific test with minimum cost.

Thyroid function tests to rule out hypothyroidism Mass or activity measurement of LPL is rarely avail-
able in routine laboratories but may be requested
Liver tests (including gamma GT) to rule out liver dis- from specialist centres. This measurement requires
ease, excessive alcohol intake and primary biliary cir- administration of 60 to 100 IU of heparin/kg to mo-
rhosis. Further liver tests such as anti-mitochondrial bilize the LPL bound to the endothelium.
antibody levels and other autoantibody screens may
be required Genetic testing is available for the diagnosis of the
condition. Additional proteins involved in LPL enzyme
Glucose and glycated haemoglobin to rule out dia- complex in lipolysis are Apo CII, Apo A5, Lipase
betes Maturation factor 1 (LMF1) and glycosylphosphatidyl
inositol anchoring high density lipoprotein binding
Protein electrophoresis may be required as the pres- protein 1 (GPIHBP1). Mutations involving these pro-
ence of monoclonal proteins can raise TG concen- teins `may result in excessive chylomicrons in the
tration circulation. Current recommendation is for full gene
sequencing of LPL and the genes for other 4 co-fac-
Investigations that establish risk and diagnosis tors involved in lipolysis

Lipoprotein related Lipoprotein(a) Type 2a hyperlipidaemia or familial hypercholestero-
laemia in addition to lipoprotein (a) and a full lipid
Apoproteins: profile most international guidelines recommend ge-
netic testing that involves sequencing of LDL recep-
apo B-100, A-I, CIII LDL particle size tor, Apo B and PCSK9 genes.

Particle number Apo E genotype Type 2b or familial combined hyperlipidaemia

Nonlipid risk factors Genetic testing is not available. A nomogram includ-
ing Apo B levels, total cholesterol and TG concentra-
1. Homocysteine* tion for diagnosis of familial combined hyperlipidae-

2. Fibrinogen

3. Plasminogen activator inhibitor

GCDC 2017

Cardio Diabetes Medicine 2017 357

mia is available but not routinely used as it has not of a Lipid Profile: Clinical and Laboratory Implications Including
been evaluated Flagging at Desirable Concentration Cutpoints-A Joint Consensus
Statement from the European Atherosclerosis Society and European
Type 3 hyperlipidaemia or dysbetalipoproteinaemia Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem.
Apolipoprotein E(ApoE) is a ligand that facilitates re- 2016 Jul;62(7):930-46.
moval of chylomicron remnant particles to the liver
through a receptor-mediated mechanism. The gene 4. Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca
for ApoE exists in 3 isoforms- 2,3 and 4. Each indi- VA, Garber AJ, Grunberger G, Guerin CK, Bell DSH, Mechanick JI,
vidual inherits 2 genes in any combination, one from Pessah-Pollack R, Wyne K, Smith D, Brinton EA, Fazio S, Davidson
each of the parents. Apo 3,3 is considered as normal. m.  american association of clinical endocrinologists and american
All others bothheterozygous or homozygous for the college of endocrinology guidelines for management of dyslipidemia
2 isoform are likely to have raised TGlevels and the and prevention of cardiovascular disease. Endocr Pract. 2017 Apr;23(-
genotype with the 2,2 isoform is pathological causing Suppl 2):1-87.
the dysbetalipoproteinaemia syndrome Ultracentrifu-
gation and isolating the beta VLDL and electropho- 5. Clinical Lipidology A companion to Braunwald’s heart disease1st Edi-
retic techniques may reveal the abnormal fraction, tion Christie M Ballantyne Saunders Elsevier SBN 978 1 4160 5469 6
but requires expertise. Electrophoresis using iso elec-
tric focusing helps differenciate the three isoforms. A
ratio of ApoB to total cholesterol below 0.15 has also
been shown to differentiate this condition from oth-
er mixed hyperlipidaemias. Apo E phenotyping using
isoelectric focusing can be set up and/or genotyping
can be made available in specialist laboratories.

No specialist investigations are available to investi-
gate type 4 or type 5 hyperlipidaemia.

It is essential to consider a diagnosis when lipid ab-
normalities present and appropriate investigations
are likely to help with a diagnosis and screening of
family members for an early diagnosis. More elabo-
rate diagnostic markers may be required in managing
these patients as many novel drugs are being investi-
gated and may require more precise diagnosis before
these drugs are administered.

References

1. Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P,
Sikand G, La Forge R, Daniels SR, Wilson DP, Morris PB, Wild RA,
Grundy SM, Daviglus M, Ferdinand KC, Vijayaraghavan K, Deedwa-
nia PC, Aberg JA, Liao KP, McKenney JM, Ross JL, Braun LT, Ito
MK, Bays HE, Brown WV, Underberg JA; NLA Expert Panel.. National
Lipid Association Recommendations for Patient-Centered Management
of Dyslipidemia: Part 2. J Clin Lipidol. 2015 Nov-Dec;9(6 Suppl):S1-122.
e1. doi: 10.1016/j.jacl.2015.09.002.. Erratum in: J Clin Lipidol. 2016 Jan-
Feb;10(1):211.

2. Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH,
McKenney JM, Grundy SM, Gill EA, Wild RA, Wilson DP, Brown
WV.  National lipid association recommendations for patient-centered
management of dyslipidemia: part 1--full report.  J Clin Lipidol. 2015
Mar-Apr;9(2):129-69. doi: 10.1016/j.jacl.2015.02.003. Epub 2015 Apr 7.
PubMed PMID: 25911072. 

3. Nordestgaard BG, Langsted A, Mora S, Kolovou G, Baum H, Bruck-
ert E, Watts GF, Sypniewska G, Wiklund O, Borén J, Chapman MJ,
Cobbaert C, Descamps OS, von Eckardstein A, Kamstrup PR, Pulkki
K, Kronenberg F, Remaley AT, Rifai N, Ros E, Langlois M; Euro-
pean Atherosclerosis Society (EAS) and the European Federation of
Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consen-
sus Initiative.. Fasting Is Not Routinely Required for Determination

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358 Cardio Diabetes Medicine 2017

ECG Evaluation in Patients with
Acute Coronary Syndrome

Dr. Senthilkumar Nallusamy*

Dr. A. Balaji**

Dr. M. Shyamala Priya***

*Chief Cardiologist, Apollo Hospital, Trichy And Rana Hospital, Trichy
**& ***Resident, Apollo Hospital, Trichy.

Introduction: ECG Criteria for Acute Stemi in The Absence
of LBBB:
The goal of the emergency department evaluation is
to determine the cause of the chest discomfort and ACC / AHA / World Heart Federation Committeepro-
promptly initiate appropriate therapy. It is essential posed the below definition of ECG criteria for diag-
that the initial ECG evaluation should be accurate and nosing STEMI:
rapid so that one can plan the treatment strategy ac-
cordingly and evidence based. New ST elevation atthe Jpoint in two contiguous
leads with >0.1 mv (1mm)in anterior leads except V2-
In general, a resting ECG should be obtained in all V3. (See figure-1)
adults with chest pain presenting to the emergency
department.ECG is the mainstay in the initial diagno- In leads V2 – V3, the following points apply:
sis of patients with suspected Acute Coronary Syn-
drome (ACS). a. >0.2 mv(2mm) in men ≥ 40 years

Usefulness of ECG: b. >0.25mv(2.5mm) in men ≤ 40 years

1. From the ECG, we can categorise patients with c. >0.15mv (1.5 mm)in women.
chestpain into one of the below three groups:
Figure -1
2. ST Elevation MI ( STEMI or new onset LBBB)

3. Non- ST Elevation MI (NSTEMI) or Unstable Angina
Undifferentiated chest pain syndrome

I. ECG in Stemi: SGARBOSSA’S ECG CRITERIA FOR
DIAGNOSING ACUTE STEMI IN THE
ECG in patients with STEMI is useful in the PRESENCE OF LBBB
following ways:-
Ecg Criteria Points
* In diagnosing
* Localising the MI
* Extent of Myocardial injury
* Age of the infarct
* To identify the infarct related artery.
* Presence of conduction defects.

St Segment Elevation Of > 1Mm 5
And Concordant With The QRS
Complex

GCDC 2017

ECG Evaluation in Patients with Acute Coronary Syndrome 359

St Segment Depression > 1Mm 3 should be repeated at least every 20 to 30 minutes.
In Leads V1,V2 Or V3 In addition to the evolution of the ECG changes in
St Segment Elevation > 5Mm 2 ACS, clinicians should also remember an uncom-
And Discordant With The QRS mon source of error which is pseudo normalisation
Complex of baseline T wave inversion during the chest pain.
A Score Of > 3 Had A Specificity So, one should always compare with the previous
Of 98% For Acute MI With LBBB available old ECG’s.

The findings of ECG in STEMI depends on the PRESENCE (OR) ABSENCE OF NEW Q
WAVES:
1. Duration - Hyperacute, Acute,Evolving or Old MI
Although STEMI is typically associated with the evo-
2. Size - Amount of myocardium affected lution of pathologic Q waves, some patients do not
develop new Q waves. The appearance of new Q
Location waves in the setting of STEMI predicts both a larger
infarct and increased mortality².
II ECG IN NSTEMI
IDENTIFICATON OF INFARCT RELATED
New horizontal or down sloping ST depression ≥ ARTERY:
0.05mv (0.5mm) in two anatomically contiguous
leads with or without T wave inversion ≥ 0.1mv (1mm) 1. INFERIOR WALL STEMI:
(See figure-2)
Inferior wall STEMI may be due to Right Coronary Ar-
Figure -2 tery occlusion (RCA) or due to Left CircumflexArtery
occlusion (LCX) (See figure-3)

If it is RCA occlusion causing inferior MI-Lead III ST
elevation will be greater than lead II³

If it is Left Circumflex occlusion -Lead II ST elevation
will be greater than lead III4 Figure-3

LOCALISING THE AREA OF INFARCT / ISCHEMIA:- IMPORTANCE OF V4R IN LOCALISING THE
ARTERY CAUSING INFERIOR STEMI (See
1. Anterior Wall: Two or more of the precordial leads figure- 4)
(V1-V6)
ST- elevation in V4R - Proximal RCA occlusion
2. Antero septal: Leads V1to V3
No ST elevation in V4R – Distal RCA occlusion.
3. High lateral – Leads LI and AVL.
ST depression in V4R – LCX occlusion.
4. Lateral – V4 to V6, LI & AVL.
(The above findings in V4R is in addition to the ST
5. Inferior wall – Leads II,III, AVF elevation in inferior leads)

6. Right ventricular – Right sided precordial leads
(Right sided leads V4R,V5R should be obtained in
patients with inferior wall infarct)

7. Posterior wall- Septal precordial leads.Posterior
leads V7, V8 and V9 may be useful if there isan evi-
dence of posterior wall infarct as suggested by prom-
inent R waves and ST depression in leads V1&V2.

IMPORTANCE OF SERIAL ECG’s:

Clinicians must be aware that the initial ECG may
NOT be diagnostic in some patients with ACS.ECG

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360 Cardio Diabetes Medicine 2017

Figure -4.V4R in inferior MI Figure- 6

2.ANTERIOR STEMI: MID LAD:

Patients with anterior STEMI usually is due to a le- (Distal to first septal but proximal to the first diagonal
sion in the left main coronary artery (or) left anterior branch)ST Elevation from V1 to V6 (See figure – 7)
descending artery. Figure- 7

a)FEATURES OF LEFT MAIN CORONARY DISTAL LAD:
ARTERY LESION:
(Distal to diagonals) STElevation from V1to V4 (See
Hall mark of left main lesion is ST elevation in aVR figure - 8)
(aVR is the least noticed lead in an ECG with ACS).
Patients with NSTEMI with ST depression in anterior Figure 8
leads with ST Elevation in aVRmay have a left main
lesion (See figure-5). It carriesa sensitivity and a spec-
ificity of 85% &80% respectively.In addition, mortality
was high with a greater degree of ST elevation in
aVR5.Figure-5

b)LOCALIZING THE LESION IN LAD6:- C) WRAP AROUND LAD

The following arethe ECG findings based on the site Simultaneous ST elevation in both the Anterior and
of LAD occlusion: Inferior leads can be due to occlusion of LAD that
is usually long, wrapingaround the apex to supply
PROXIMAL LAD: the distal inferiorwall which is referred to as “wrap
around” LAD7. (See figure - 9)
(Proximal to the first septal) ST Elevation from V1toV6,
L1, AVL with complete right bundle branch block. (See
figure- 6)

GCDC 2017

ECG Evaluation in Patients with Acute Coronary Syndrome 361

Figure 9

SUMMARY:

From the ECG evaluation in patients with Acute Cor-
onary Syndrome.
1. One can diagnose whether it its due to STEMI or
NSTEMI
2. Plan the treatment strategy accordingly
3. Prognosticate based on localising the infarct re-
lated artery.

REFERENCES:-

1. TabasJA, Rodriguez RM, Seligman HK, Goldschager NF. Electrocardiograph-
ic Criteria for detecting acute myocardial infarction in patients with Left
Bundle Branch Block. Ann EmergMed. 2008;52(4):329.

2. Barbagelata A, Califf RM, Thrombolysis and Q wave versus non- Q wave
first acute myocardial infarction;a GUSTO-I sub study. J Am CollCarodiol
1997;29(4):770.

3. Zimetbaum PJ, Krishnan S,GoldA.Usefulness of ST-Segment elevation in
lead- III exceeding that of lead II for identifying the location of the to-
tally occluded coronary artery in inferior wall myocardial infarction. Am J
Cardiol.1998;81(7):918.

4. Zimetbaum PJ, Josephson ME. Use of the electrocardiogram in acute
myocardial infarction . N Engl J Med.2003;348(10):933.

5. Yamaji H, Iwasuki K, Kusachi S. Prediction of acute left main coronary
artery obstruction by 12- leadelectrocardiography. ST Segment elevation
in lead aVR with less ST segment elevation in lead V1.J Am Collcardiol.
2001;38(5):1348.

6. Engelen DJ, Gorgels AP, Cheriex EC.Value of the electrocardiogram in lo-
calising the occlusion site in the left anterior descending coronary artery
in acute anterior myocardial infarction. J Am Coll cardiol.1999;34(2):389.

7. Sasaki K, Yotsukura M, Sakata K. Relation of ST – Segment changes in
inferior leads during anterior wall acute myocardial infarction to length
and occlusion site of the left anterior descending coronary artery. Am J
Cardiol;87(12):1340.

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362 Cardio Diabetes Medicine 2017

Strain and Strain Rate Imaging in Early De-
tection of Ventricular Systolic Dysfunction -

is This The Best Investigation?

Dr. R. Balamurugan., MD DM(cardio)

Asst.. Prof Dept. Of Cardiology, TKMCH

Abstract tion. Apart from 2D the various other modalities used
over the last three decades are 3D echo,cardiac MRI
Echocardiographic assessment of LV function plays and multislice CT which were limited by expensive-
a crucial role in day to day clinical practice.Apart from ness , loading conditions and geometric assumptions
the traditional methods ,newer echocardiographic .Later it was recognised that non invasive evaluation
techniques and deformation imaging utilizing strain of myocardial tissue deformation(Strain) analysis by
and strain rate measurements by Tissue Doppler and tissue Doppler study and speckle tracking methods
speckle tracking methods gives better understand- has potential advantage of more reproducible and
ing for evaluation of the complex cardiac mechan- independent of load and geometric assumptions.
ics.The various types of strain imaging longitudinal,
circumferential and radial strain measurements is Standard Methods For Evaluation of LV
useful and got a lot of clinical applications in early Systolic Function
detection of myocardial and pericardial diseases.This
innovative technique should be part of other tradi- Traditional echocardiograhic measures of LV systolic
tional echocardiographic parameters to have a better function are M-mode, two dimensional (2D) exam-
understanding of cardiac function in different clinical inations for dimensions and Doppler derived ejection
settings. This review describes about the fundamen- indices for ventricular performance. 2D Echocar-
tal concepts of speckle tracking in obtaining strain diograhic measures of LV systolic function includes
measurements,their clinical applications and useful- ejection phase indices like fractional shortening (FS)
ness in early detection of LV dysfunction. , ejection fraction (EF) and Doppler derived echocar-
diograhic measures of LV systolic function includes
Key words: changes in peak and mean pressure over time (Δp/Δt)
and systolic time intervals.
S-Strain,SR-Strain rate,LS-Longitudinal strain,CS-Cir-
cumferential strain,RS-radial strain,STE-Speckle EF calculation by modified Simpson’s rule with bi-
tracking echo,TDI-Tissue Doppler imaging plane planimetry of LV is currently recommended [1]

Introduction Important Limitations of Ejection Fraction

Assessment of LV systolic function plays an im- Global LV systolic function by EF carries an important
portant role in prognostic and therapeutic aspects limitations due to its dependence on instantaneous
of most other acquired diseases. Echocardiogram a loading conditions, reproducibility, and low sensitivity
simple clinical tool used since long back in estimat- in detecting subtle LV systolic impairment [1].
ing the LV systolic function.Initial attempts used only
linear measurements,later 2D methods used area The EF was primarily introduced in order to charac-
and volume calculations to asses LV function.These terize the reduced myocardial function in dilated LV,
methods however had lot of drawbacks as linear but becomes inaccurate in the cases of reduced end
measurements(M Mode) provide information regard- diastolic volume (EDV), as well as severe myocardial
ing dimention and contractility along a single line only hypertrophy as in cases of “Heart failure with pre-
in a heart with regional variation in shape and func- served EF (HFPEF)” [1-3]

GCDC 2017

Strain and Strain Rate Imaging in Early Detection of Ventricular 363
Systolic Dysfunction - is This The Best Investigation?

New Methods For Evaluation of LV Systolic Decrease of the dimension (shortening of the wall in
Function longitudinal direction during systole, or decrease of
the circumferential dimension during systole, as well
Newer echocardiographic techniques, such as TDI as thinning of the wall during diastole) is marked with
and deformation imaging gives better understand- a negative number ( negative sign –) and increase
ing and evaluation of the complex mechanism of of the dimension (lengthening of the wall in a lon-
cardiac contraction and relaxation. Evaluation of LV gitudinal direction during diastole, or increase of the
longitudinal systolic dynamics has become crucial in circumferential dimension during systole, as well as
the assessment of LV systolic function and superi- thickening of the wall during systole) is marked with
or value in comparison with traditional measures [4] a positive number ( positive sign +).
and is evaluated using Tissue Doppler and speckle
tracking techniques utilizing strain (S) and strain rate Types of Strains
(SR) imaging thus giving a more detailed information
on LV systolic function and also early detection of 1.Longitudinal strain: It is the deformation or shorten-
myocardial dysfunction also. [4] ing of the myocardium in longitudinal direction during
systole .Thus this deformation is negative longitudi-
Strain and Strain Rate nally and usually varies between -15 %and -20% [11]
Figure-1
In order to understand the concept of Srain (S) and
Strain rate(SR), one should be aware of the term of 2. Circumferential strain:
deformation. During the heart cycle ventricular walls
are moving in different directions and with different It is the deformation or shortening of the myocardium
velocities, meaning that the ventricular walls and the in circumferential direction during systole.Thus this
heart are deforming. deformation is also negative circumferentially and
varies between -20 % and -25 %. Figure 2
Generally, during systole, the base of the heart
moves toward the apex in longitudinal, circumfer-
ential, radial or transmural directions. Also different
segments of myocardium move with different veloc-
ities. For instance, the basal segment of ventricular
walls moves faster than the middle or the distal seg-
ments and subendocardial myocardium moves faster
than subepicardial creating a transmural velocity gra-
dient [5]. The result of that entire phenomenon is a
deformation of the myocardium, as well as the heart.
Ventricular wall deformation can be shortening and
lengthening, and thickening and thinning. [6]

This deformation analysis mainly provides informa-
tion about regional and global myocardial function.It
is possible to analyze deformation in all three direc-
tions, longitudinal, circumferential and radial.

Regional strain is a dimensionless measurement of
deformation, expressed as a fractional or percentage
change from an object’s original dimension also de-
scribed as the amount of shortening or stretch in the
tissue It is expressed as percentage.[11]

Strain rate is the measure of rate of this deformation
or the speed at which the deformation(strain) occurs
and expressed as per second( s -1). Also SR is the
velocity motion of one part of the wall, which is cal-
culated from the difference between the velocities
of surrounding parts of myocardium, As a spatial
derivative of velocity,strain rate provides increased
spatial resolution for precise localization of diseased
segments.

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364 Cardio Diabetes Medicine 2017

Figure 2 Techniques of Performing Strain Imaging

Speckle Tracking Echocardiography-Based Peak Systolic Strain 2D Echo in apical plane( Apical 4 chamber,three
Measurements (A) Global longitudinal strain (GLS), (B) global chamber and two chamber views) for longitudinal
radial strain (GRS), and (C) global circumferential strain (GCS). strain and shot axis plane for circumferential and ra-
The left panels show the direction (arrows demonstrate the dial strain quantification are used.3 to 4 ECG gated
direction) in which various strain parameters are being measured. consecutive cardiac cycles at a frame rate of 60-100
The middle panels demonstrate the segmental strain values frames per second in a high quality echo image with
(except for circumferential strain). The right panels illustrate the clear endocardial epicardial differentiation is used.
regional strain curves. Circumferential strain curves in the bottom The speckles are tracked by semi automated tracking
right panel highlight the segmental variability in measurements, algorithm and the myocardial deformation computed
illustrating the challenges with this specific strain measurement and represented graphically as longitudinal,circum-
ferential and radial strains.
AVC = aortic valve closure.
The maximum and average strains during systole
3. Radial strain : are termed Peak systolic strain and Mean systolic
strain respectively.Similar to strain curves strain rate
It is the thickening or lengthening of myocardium ra- curves are also negative at peak systole and positive
dially during systole.Hence it is positive radially and in diastole.The longitudinal strain analysis performed
varies between 30% and 40% . Figure 1 in apical views with the aid of software automatically
generates a topograohic representation of all 17 ana-
Methods of Strain Imaging lysed segments(Bull s eye).[7]

There are two methods for SR and S imaging , colour Clinical applications of speckle tracking echo
TDI and speckle-tracking in 2D greyscale images. The
first one is based on color TDI with the determination The estimation of LS,CS,RS provide an early and
of velocities in predefined wall regions. This method accurate assessment of different myocardial and
is complex as the operator should be well-trained, pericardial diseases.[4,11]
with different software solutions and results in sig-
nificant interobserver variability. [7] 1.Myocardial diseases

Another method, 2D speckle-tracking, is based on LS is governed by subendocardial region and is a
greyscale images. The basic principle is based on the vulnerable and sensitive marker for myocardial pa-
normal presence of an irregular , random , speckled thology.Impaired LS could be the first indicator of
pattern in myocardium, with those speckles following myocardial pathology even when ejection fraction is
the motion of myocardium.[10] normal. The longitudinal strain provides a quantitative
myocardial deformation analysis of each LV segment
STE, Specle tracking echo has recently emerged as a and detecting early systolic dysfunction in patients
quantitative ultrasound technique for accurately eval- with preserved LVEF.[12]
uating myocardial function by analyzing the motion
of speckles (spots generated by the interaction be- 2.Pericardial diseases
tween ultrasound beam and myocardial fibres iden-
tified on 2D echo. CS is governed by subepicardial region and are the
first to get affected in pericardial diseases like con-
Newer methods of speckle tracking for calculation strictive pericarditis.Also the global CS is the power-
of strain or strain rate involves evaluation of myocar- ful predictor of cardiac events in heart failure with
dial region with reference to an adjacent myocardial reduced EF.
segment rather than to a fixed transducer position.
3.Diabetes
It provides a non Doppler,angle independent,objec-
tive quantification of myocardial deformation and LV Asymptomatic diabetic patients with preserved LVEF
systolic and diastolic dynamics with interobserver ,STE has the potential for detecting subclinial LV sys-
and itraobserver reproducibility and high feasibility. tolic dysfunction which is unmasked by the alteration
[7] of longitudinal strain.Thus STE detects early detection
of development of subclinical myocardial dysfunction
By tracking the displacement of speckles during car- in diabetic patients before the overt appearance of
diac cycle,strain and strain rate can be rapidly mea- diabetic cardiomyopathy.[8]
sured offline after good image acquisition[10]

This method is easier to perform, allows immediate
quantification and is, therefore, more suitable for ev-
eryday clinical practice.

GCDC 2017

Strain and Strain Rate Imaging in Early Detection of Ventricular 365
Systolic Dysfunction - is This The Best Investigation?

4.Coronary Artery Disease for evaluating right ventricular function or function of
hearts with single-ventricle physiology.
Reduced LS values in asymptomatic patients even
without wall motion abnormalities is a strong pre- In contrast to only EF analysis,new speckle tracking
dictor of stable ischemic cardiomyopathy.LS after echocardiogram utilizing strain ,strain rate parame-
reperfusion therapy is an excellent predictor of LV ters have shown to reliably detect preclinical abnor-
remodelling and adverse events.LS also correlates malities in both regional and global myocardial func-
well with regional extent of scar tissue as evaluated tion at an early stage .[9]
by contrast MRI.[12]
Limitations of Strain,Strain rate imaging
A cuttoff value of -4.5 % for regional LS discriminates
between viable myocardium and scar tissue.[3] Stain measurements are not possible in non sinus
rhythms.
The postsystolic motion or index measured after aor-
tic valve closure is an important quantitative marker STE requires good image acquisition to delineate
for analysis of ischemic myocardium. endocardial border

In transmural pathologies like myocardial infarction The STE technique results depend critically on the
where epi,mid and subendocardial functions are uni- machine with which the analysis are made and they
formly affected and all LS,CS,RS show significant im- are not interchangeable among different manufac-
pairement.[3] tures.

5.Heart Failure And Dyssynchrony The tissue Doppler derived strain and strain rate has
a limitation of angle dependency,noise interference ,
STE plays a vital role in understanding mechanics inter intra observer variability and strict dependence
of heart failure.Decreased LS but preserved apical on frame rate[7]
rotation mechanics and variable CS and RS are the
hallmark Heart failure with preserved EF.When the These parameters are technically more challenging
HF syndrome progress from diastolic to systolic dys- and require further standardizations.Further stud-
function the LV torsion and peak untwisting rate are ies are required to assess the incremental value of
valso reduced.[12,4] strains acquired from 2D /3D datasets Prospective
clinical trials for validation of this technique in large
6.Dilated Cardiomyopathy populations are still lacking.

DCM has shown impairement of all three strains(LS Conclusion
,CS and RS) and also decrease in apical twist and
untwisting velocity. Strain imaging is an innovative technique for objec-
tively quantifying myocardial mechanics. Quantifica-
7.Stress Cardiomyopathy tion of LS,RS,CS allows an accurate and reproducible
assessment of segmental and global LV/RV function.
It is a form of reversible LV systolic dysfunction with LS has been found to be the most useful and easy
transient apical ballooning.Here STE shows reduction parameter obtained from apical views.
in various strains extendind beyond any single arteri-
al territory,also with reduced peak systolic strain and STE is more comprehensive, feasible and reproduc-
strain rate in apical and basal regions differentiating ible.
Stress Cardiomyopathy from ACS.
Echocardiography is currently the most widely used
Advantages of Strain,Strain rate imaging method in the assessment of ventricular function.
Besides the traditional methods, , newer techniques
Deformation imaging techniques (SR and S) have should be introduced in clinical routine .Strain ,Strain
some important advantages over the standard ECHO rate imaging is thus one amoung the best investiga-
techniques. The main benefit of regional S and SR tion in early detection of LV dysfunction There is no
lies in the rapid and objective detection of regions single ideal technique or parameter for this purpose,
with delayed or decreased deformation, while for tra- so the combination of several of the other parame-
ditional echocardiographic methods, one has to de- ters is also necessary in order to have more compre-
pend on subjective assessment for this information. hensive information about different aspects of heart
function in different clinical settings
Another advantage of this technique is its indepen-
dence of ventricular geometry,therefore, it is suitable

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366 Cardio Diabetes Medicine 2017

References

1. Devereux RB, Roman MJ, Palmieri V, Liu JE, Lee ET, Best LG, et al.
Prognostic implications of ejection fraction from linear echocardiographic
dimensions: the Strong Heart Study. Am Heart J. 2003;146(3):527–34.

2. Palmieri V, Roman MJ, Bella JN, Liu JE, Best LG, Lee ET, et al. Prognostic
implications of relations of left ventricular systolic dysfunction with body
composition and myocardial energy expenditure: the Strong Heart Study.
J Am Soc Echocardiogr. 2008;21(1):66–71.

3. Picard MH, Wilkins GT, Ray PA, Weyman AE. Natural history of left
ventricular size and function after acute myocardial infarction. Assess-
ment and prediction by echocardiographic endocardial surface mapping.
Circulation. 1990;82:484e94.

4. Zaca V, Ballo P, Galderisi M, Mondillo. Echocardiography in the assessment
of left ventricular longitudinal systolic function: current methodology and
clinical applications. Heart Fail Rev. 2010;15:23–37.

5. Wilkenshoff UM, Sovany A, Wigstrom L, Olstad B, Lindstrom L, Engvall J,
et al. Regional mean systolic myocardial velocity estimation by real-time
color Doppler myocardial imaging: a new technique for quantifying regional
systolic function. J Am Soc Echocardiogram.

6. Buccheri S,Monte I,Mangiafico S,et al.Feasibility,reproducibility and
agreement between different speckle tracking echocardiographic tech-
niques for the assessment of longitudinal deformation.Biomed Res
Int.2013,2013:297895

7. Kaluzynski K, Chen X, Emelianov SY, Skovoroda AR, O’Donnell M. Strain
rate imaging using two-dimensional speckle tracking. IEEE Trans Ultrason
Ferroelectr Freq Control. 2001 Jul;48(4):1111–23.

8. Ng AC,Delgado V,Bertini M,et al.Findings from left ventricular strain and
strai rate imaging in asymptomatic diabetic patientswith type 2 diabetes
mellitus.Am J Cardiol2009;104:1398-1401

9. Mori K, Hayabuchi Y, Kuroda Y, Nii M, Manabe T. Left ventricular wall
motion velocities in healthy children measured by pulsed wave Doppler
tissue echocardiography: normal values and relation to age and heart rate.
J Am Soc Echocardiogr. 2000;13:1002–11

10. FriedbergMK, Mertens L. Tissue velocities, strain, and strain rate for
echocardiographic assessment of ventricular function in congenital heart
disease. Eur J Echocardiogr. 2009;10:585–93

11. Feigenbaum“s Echocardiography seventhedition,WilliamF.Armstrong,
Thomas Ryan-Evaluation of systolic function of LV-Chapter 6

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Cardio Diabetes Medicine 2017 367

Cardiac MRI vs PET Scan

Dr. G. N. Mahapatra

Senior Consultant & Head, Dept of Nuclear Medicine,
PET-CT & SPECT-CT

Seven Hills Hospital (JCI USA accredited), Mumbai.

Introduction : Clinical Uses in day to day Practice:

CAD is among the major public health issues across Cardiac MRI (CMR) is a non-invasive diagnostic tool
the globe & is still largely perceived as a conse- which can be used for morphology , function, viability
quence of the incremental occlusion of coronary & perfusion assessment in coronary artery disease
arteries through progressive vascular stenosis that (CAD) & other important infiltrative diseases of the
can be diagnosed by coronary angiography & treat- myocardium .
ed by percutaneous or surgical coronary revascular-
ization. Today an unreasonable a large number of Clinical Uses of Cardiac MRI Vs PET Scan in
symptomatic & asymptomatic at risk patients with CAD :
suspected CAD with risk factors such as diabetes
mellitus, hypertension, dyslipidemia, tobacco smok- i)Rest & Stress CMR myocardial perfusion imaging
ing /consuming either through Paan or cigarettes (MPI) Vs PET Stress –Rest MPI.
will undergo coronary angiography . Another subset
of patients having 100% blockage in the major cor- ii)LGE or dobutamine stress CMR Vs PET F-18, FDG or
onary arteries has been also revascularized without Rb-82 or N-13 Ammonia, radiotracers in the assess-
accessing myocardial viability. Several large ran- ment of myocardial viability.
domized trials have emphasized the limitations of
coronary arteriography studies that lead to thera- Clinical Uses of Cardiac MRI Vs PET Scan in infiltrative
peutic interventions based only on the morphologic Cardiac Diseases.
severity of epicardial coronary stenosis, these trials
advocate for additional proof of haemodynamically i)Cardiac MRI Vs PET Scan in sarcoidosis ,Amyloido-
significant stress induced reduction in coronary flow sis, Tuberculosis.
before any therapeutic interventions are undertaken.
At the clinician’s disposal is a large armamentarium 1.Rest & Stress CMR Myocardial Perfusion
of tests including treadmill stress test, stress MPI, Imaging (MPI) Vs PET Stress-Rest MPI :
stress ECHO, stress PET, CT coronary angiography &
cardiac magnetic resonance imaging (CMR). Though CMR is a non-invasive diagnostic stool that does not
all are available for the diagnosis & prognostication require ionizing radiation & can be used to assess
of patients with suspected and documented coronary myocardial perfusion abnormalities using Gadolini-
artery disease (CAD) , selecting the “best test” can um based contrast agent in a dose of 0.1 mmol/per
be daunting to clinicians. And understanding of the Kg of body weight at a rate of 5ml/min. This agent
patient population, patient pretest probability of CAD has very low nephrotoxicity. Immediately after the
, the risk benefits and limitations of each technology injection of the contrast agent, images for myocar-
will enable the medical imaging professional to assist dial perfusion study is obtained. After a gap of 10-15
clinicians with test selection. minutes , i.v. Adenosine infusion with 140 mg/Kg/
min for period of 3 minute is administered following
which Gadolinium DTPA is injected at a rate of 0.1
mmol/per Kg of body weight at a rate of 5ml/min,
followed by 3 min of adenosine infusion is continued.
Late Gadolinium enhancement (LGE) imaging study

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368 Cardiac MRI vs PET Scan

can be acquired after 5-10 min. Only disadvantage Tracers of Metabolism
of the study is the absence of LV contour with ab-
sence of absolute quantification of CMR measured 11C- palmitate Fatty acid metabolism
myocardial perfusion with only visual assessment of
rest & stress CMR. 18-F-FDG Exogenous glucose me-
tabolism
However CMR , MPI & LGE may provide complemen-
tary prognostic information in patients with known or 11C-acetate Oxidative metabolism
suspected CAD & hence LGE imaging is a necessary
part of a comprehensive approach towards evalua- 150-oxygen Oxygen consumption
tion.
11C (13N) amino acid syn- Amino acid and protein
However pacemakers, implantable Cardiac defibril-
lators are still considered as a contraindications to thesis metabolism
CMR. However MRI compatible devices are available
& are just being used in few centers only. Further Other tracers
more , claustrophobia remains an issue compared
to other imaging methods . 18F-misonidazole Hypoxic and ischemic
tissue
Imaging artifacts such as dark rim & inadequate cov-
erage of the ventricle are limitations for CMR. 11C- carbon monoxide Blood pool

Gadolinium based contrast agents are used for MPI. PET CT unit has become the preferred approach for
This agent has very low nephrotoxicity & they are PET imaging in oncology. The potential benefits of
contraindicated in patients with severe impaired renal PET-C The most commonly used radiopharmaceutical
function due to risk of nephrogenic fibrosis. for cardiac PET imaging are F-18 FDG, Rubidum-82
Chloride, N-13 ammonia, O-15 water.
Absolute quantification using any software unlike
nuclear or PET imaging of CMR measured myocar- Injury to the myocardium is typically caused by de-
dial perfusion has yet to be implemented in clinical creased blood flow, a consequence of arterioscle-
practice. rosis. Such evaluations involve monitoring regional
coronary blood flow & ongoing active metabolism.
PET Stress-Rest Myocardial Imaging (MPI) : These procedures can help identify potential viability
of injured myocardium, regions likely to benefit from
Positron Emission Tomography techniques are em- revascularization to facilitate its return to its normal
ployed to map myocardial perfusion & detect isch- function for e.g. PET study showing increased glucose
emic response to stress in the presence of coronary consumption (using F-18 FDG) in myocardial areas of
artery disease, quantitate the regional coronary blood decreased blood flow (using N-13 ammonia or Rb-82)
flow which can identify diffuse atherosclerosis often would indicate that restoration of cardiac function in
undetectable on an angiogram & in the assessment those areas would be possible. Impaired contractile
of myocardial tissue viability. function in response to chronic reduction of resting
blood flow may mask myocardial viability in some
Table patients with severe CAD with the use of O-15 water,
cardiologists obtain images of artery walls, where live
tissue is designated by areas of illumination caused
by high oxygen consumption.

POSITRON EMITTING ISOTOPES USED IN CARDI- Tracers of Myocardial Perfusion:
AC PET
Positron emitting radionuclides used for assess-
CATEGORY COMPUNDS FUNCTION ment of regional perfusion can be classified into two
(MECHANISM) groups:

Tracers of Blood Flow Tracers that are only partly extracted by the myocar-
dium (Rb-82 chloride & N-13 ammonia) &
13-N ammonia Metabolic trapping
Tracers that are freely diffusible (O-15 water)
82Rb Sodium-Potassium
Pump Stress Rubidium-82 PET myocardial perfusion study.

150-water Diffusion Myocardial perfusion imaging with positron emitter
can be done without onsite cyclotron which is rela-
62 Copper PT SM Lipophilicity tively complicated with an onsite source of generator
produced tracer i.e Rubidium-82.
11C (gallium 68) albumin Capillary blockage
microsphere

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Rb82 is a monovalent cation and has ultra short base at the rim. Both relative and absolute flow re-
half life 75 sec. Sr-82 decays to an elution column. serve can be depicted on quantitative polar maps on
Rb82 is eluted with 25 to 50 ml of normal saline by Rb82 activity. In this manner the rest and stress imag-
a computer controlled elution pump, connected by es are functionally interrelated. Three dimensional (3-
IV tubing to the patient. This generator has almost D) topographic displays of Rb82 cardiac activity are
no breakthrough of strontium and has useful life of more quantitative with respect to the polar maps. An
4-6 weeks. Serial evaluations of regional myocardi- automated quantitative analysis programmed may
al perfusion can be made at intervals as short as 5 enhance accuracy and reproducibility of cardiac PET
minutes. The short half life of Rb82 taxes the perfor- flow studies.
mance limits of PET scanners; it facilitates the rapid
completion of a series of resting and stress myocar- The sensitivity and specificity of PET MPI are superi-
dial perfusion studies. Rb-82 is a very efficient imag- or to other non-invasive tests. Four studies involving
ing agent for routine clinical usage. Although the cost a total of 342 patients have made direct comparisons
per patient at a low volume of studies per day is high, of Tl-201 SPECT and PET MPI. In addition a survey of
the cost with 6 to 10 studies per day is competitive numerous studies of PET MPI in 1391 patients found
with SPECT tracers. excellent sensitivity (92%: C I = 90% to 94%) and spec-
ificity (90% C I = 88% to 92%). Church well et al has
The first pass extraction of Rb-82 at rest is approx- also shown greater accuracy in a blinded analysis of
imately 50-60% and it’s via Na+/K+ AT pase pump. the accuracy of 82 Rb PET in 194 patients with new
Myocardial extraction of Rb-82 is similar to thallium quantitative software developed in their laboratory.
– 201 and slightly less than N-13 ammonia, decreasing Patterson et al has also shown significantly better
during hyperemia .Rb- 82 extraction can be altered results with 82-Rb PET than their own SPECT Tl-201
by severe acidotic hypoxia and ischemia. (36). Thus results. These comparisons and Emory University’s
uptake of Rb-82. is a function of both blood flow and extensive clinical experiences (over 30,000 SPECT
of myocardial cell integrity. Rb-82 perfusion imaging Tl-201 and over 2000 MPI. Though all patients with
is usually performed before and after vasodilator intermediate risk of coronary artery disease can un-
stress rather than with exercise. Infracted myocar- dergo PET MPI, it is preferable to SPECT MPI in a
dium doesn’t retain intravenously administered Rb- subgroup of patients with attenuation problems i.e
82. After administration, it washes out rapidly from large patients, women, breast implants or left mas-
damaged myocardial cells following the initial uptake tectomy, chest wall deformity, left pleural or pericar-
phase. A mixture of reversible and irreversible myo- dial effusion. However it must be emphasized that
cardial tissue in the field of view results in an inter- attenuation problems in SPECT can not be predicted
mediate level of Rb-82 wash out that is proportional with confidence from examination of body habitus.
to the percentage of viable or infracted tissue. There is an incremental benefit caused by greater
specificity and sensitivity which gives rise to incre-
Imaging of Rb-82: mental economic benefit caused by more accurate
tests like Rb82 PET MPI.
Patient preparation for stress and rest myocardial
PET perfusion imaging is identical to SPECT perfu- During the last 10 to 15 years ,both SPECT and PET im-
sion imaging. Despite the short half-life of Rb82, aging have undergone significant improvements . A
modern PET gamma cameras are able to obtain good recent comparison between Tc-99m sestamibi SPECT
quality images. The usual protocol takes approxi- and Rb82 PET MPI revealed a significant margin of
mately 15 minutes with a BGO crystal PET scanner improvement for CAD detection accuracy with Rb82
and 35 minutes with LSO crystals PET scanner. The PET compared to SPECT (38). Given the proven value
proper positioning is done with a low dose (20mci) of PET myocardial perfusion imaging in the diagnosis
injection of Rb-82 and short 3 minutes scout acqui- of CAD, it is expected that the prognostic value of
sition and quick reconstruction. Subsequently, rest gated PET is also high, similar to SPECT imaging.
transmission imaging, rest perfusion 2D imaging and
rest gated 3D imaging were done sequentially. Stress T in cardiac imaging is reduction in acquisition time
imaging is also done in similar manner. Transmission by 10-12 minutes in comparison to a dedicated PET
imaging is usually done with a germanium-68 pin or system. PET-CT imaging holds challenges and solu-
rod source, which takes about 8 minutes.
tion for the attenuation correction problem.
Tomographic data from Rb82 images can be dis-
played using polar maps utilizing the bulls eye ap-
proach with the apex located at the centre and the

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370 Cardiac MRI vs PET Scan

Rubidium-82 PET myocardial perfusion image show- Intense F-18 FDG uptake in the lateral and inferior
ing defect involving inferolateral segment with evi- segment of the myocardium suggestive of hibernat-
ing myocardium.
dence of reversible ischaemia.
Stress F-18 FDG PET myocardial ischemia
Stress N-13 Ammonia/O-15 labelled water PET Perfu- imaging:
sion Imaging
Direct myocardial ischemia imaging using FDG ra-
13 N ammonia has been used for most of the sci- dionuclide myocardial perfusion imaging during ex-
entific investigation in cardiac PET imaging for the ercise or pharmacological stress and at rest is the
past two decades. Its 10 minutes half –life requires most widely used non-invasive test for evaluation
an onsite cyclotron and radiochemistry synthesis of known or suspected CAD. This technique relies
capability. Imaging protocol from scout position to on the demonstration of perfusion abnormalities on
stress imaging takes 100-120 mins. Pharmacologic stress images which normalize on rest images in the
stress imaging usually follows resting injection and presence of myocardial ischemia, but persist in the
imaging, after the initial activity has been allowed presence of scar due to prior myocardial infarction.
to decay by staggering patients or using differential Myocardial ischemia results in a dramatic and sus-
dose for rest and stress. Both rest and stress images tained switch to glucose uptake. At myocellular level,
can be gated. A dynamic acquisition is acquired for hypoxia results in an up regulation and translocation
the quantification of blood flow. This can be accom- of glucose transporters from cytosol to the cell mem-
plished by performing separate dynamic and gated brane .Once activated, these transporters remain
acquisition with the same injection, or included list upregulated for several hours. In contrast, normal
mode acquisitions .A third injection may be included myocardium is capable of utilizing a wide variety of
for cold pressor testing. 13N ammonia imaging is time substrates for its energy requirements, depending
cumbersome, needs logistic and coordination. upon their blood levels, insulin and catecholamine
levels and or fasting status of individual. Fatty acids
13N ammonia allows good quality gated and ungated are normally the preferred substrate for energy pro-
images, taking full advantage of the superior resolu- duction, with glucose contributing to less than 40%
tion of PET imaging .Interestingly normal volunteers of total energy production .The differential uptake
show mild heterogeneity or mild defect of 13N am- of glucose in ischemic and normal myocardium can
monia retention in the lateral wall of the left ventricle help develop “hot spot” imaging agent for myocardi-
compared with other segments. The mechanism of al ischemia. Fluorine-18(18F) labeled 2-deoxyglucose
this is not known. This must be taken in to account (18FDG) is a glucose analogue, which tracks the ini-
for both visual activity and increased lung activity in tial steps of glucose transport and uptake across the
patient with lung congestion. cell membrane .Once, in the cell this is phosporylated
by hexokinase to 18FDG-6-phosphate similar to glu-
cose. However, unlike glucose-6-phosphate cannot
be phosporylated further and because of its strong

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negative charge, 18FDG-6- phosphate is trapped in- Weishaowu
tracellularly.
Stress F -18 FDG ischaemia imaging showing intense F-18 FDG uptake in the inferior &
The feasibility and accuracy of exercise 18FDG im- lateral walls of the myocardium which was showing a fixed defect in the regular stress
aging for hot spot imaging of exercise induced & rest myocardial perfusion imaging.
myocardial ischemia was studied by performing si-
multaneous exercise perfusion and 18FDG imaging Stress F-18 Flurpiridaz Myocardial Perfusion
in patient scheduled to undergo exercise and rest Imaging :
myocardial perfusion imaging for suspected CAD.
All patients underwent a symptom –limited exercise Flurpiridaz F-18 a new PET MPI radiopharmaceuti-
after an overnight fast. 99mTc-sestamibi (25mci) and cal in phase III clinical trial for detection of CAD. It
18FDG (8-10mCi) were injected iv at peak exercise. is a structural analog of pyridaben and binds to mi-
The patients underwent imaging using a dual-head tochondrian complex I with high affinity. Preclinical
large field of view single –crystal SPECT imaging cam- studies show that the extraction fraction of flurpiridaz
era (varicam ,GE ,Milwaukee,USA) equipped with ul- F-18 was greater than 90%. The positron range of F-18
tra –high energy parallel hole collimators and 5/8” is approximately seven times shorter than that of RB-
thick sodium iodide crystal to optimize the detection 82, so it would be accepted to produce images with
of high-energy(511KeV)18F photons. Use of separate higher resolution. With a longer half-life, 18 F-labeled
energy window of 99m Tc (140+20%) and 18F (511+30) flurpiridaz may be produced at regional cyclotrons
allowed simultaneous imaging of 99mTc-sestamibi and delivered to imaging centers in much the same
and 18FDG. The results of exercise 18FDG imaging way as F-18 labeled FDG thus ,obviating need for an
were compared with those of standard onsite cyclotron. The longer half-life of F-18 also en-
sures that the radiotracer is present long enough to
exercise and rest myocardial perfusion imaging and allow a patient injected at peak treadmill exercise to
coronary angiography. move to the camera and still be effectively imaged.
Higher myocardial extraction facilitates detection of
Intense F-18 FDG uptake seen in the lateral wall of the segments milder perfusion defects and allows more accurate
quantification of myocardial blood flow (MBF).
Short Axis
Ex A higher percentage of images were rated as ex-
cellent/good on PET versus SPECT on stress (99.2%
R Vs88.5%) and rest (96.9% Vs 66.4%) images diag-
nostic certainty of interpretation was higher for PET
Vertical Long Axis Horizontal Long Axis versus SPECT (90.8% Vs 70.9%). In 86 patients who
Ex underwent invasive coronary angiography, sensitiv-
ity of PET was higher than SPECT (78.8% Vs 61.5%
R respectively). Specificity of was not significantly dif-
ferent (PET 76.5% Vs SPECT 73.5%).
gx Jain et al
The overall quality of the PET images was superior to
intense FDG uptake seen in the lateral and inferior myocardial segments as compared the TC-99 SPECT images. Flurpiridaz F-18 PET imag-
to no stress perfusion defects seen in stress MPI in the Ist row of images. es showed severe anterior and apical defects in the
distribution of the diseases CAD coronary artery, but
the TC-99 SPECT images showed only a small mild
anteroapical defect.

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372 Cardiac MRI vs PET Scan

TC-99m SPECT images and flurpiridaz F-18 PET imag- MRI has distinctive unique ability to assess viable
es from patients with a low likelihood of CAD: a false and infarcted myocardium by different techniques as
positive partially reversible inferior defect is present one-stop shop. MRI techniques have the advantage
on the TC-99m SPECT images due to soft-tissue at- of no ionizing radiation. Owing to its superior spatial
tenuation. The flurpiridaz F-18 PET study, however , resolution, CMR (Cardiac magnetic resonance) has
provided superior images quality and was normal. a unique capability to assess small infarcts and to
measure the transmural extent of MI. Therefore, it
Absolute Quantification of Myocardial Blood can detect microinfarcts associated with successful
Flow : coronary angioplasty, as well as the detection of sub-
endocardial infarcts which could be missed by SPECT
The results of absolute quantification of MBF with or do not exhibit a wall motion abnormality.
flurpiridaz F-18 PET represents a major advantage
over SPECT MPI, and is potential game- changer in There are 3 main techniques to assess myocardial
the noninvasive evaluation of CAD. Studies with 13 viability; resting MRI (to measure end diastolic wall
NH3 , H215O and Rb-82 have shown that absolute thickness),dobutamine MRI (to evaluate contractile
quantification of MBF allows better identification of reserve),and contrast enhanced (delayed enhanced)
multivessel disease, allows evaluation of endotheli- MRI [DE-MRI] to detect the extent and transmurality
al dysfunction and responses to treatment and has of scar tissue)
incremental value in prognostication in patients with
suspected or known CAD. Assessment of resting wall thickness and thickening
by resting cine-MRI Can be used to assess viability
. The underlying hypothesis is that regions of myo-
cardial thinning reflect chronic myocardial infarction.
The combination of wall thickness and systolic wall
thickening tend to improve the sensitivity and spec-
ificity of the technique. Cine-MRI performed during
dobutamine infusion can be used assess potential
for contractile response to coronary revascularization
with diagnostic performance at least comparable to
dobutamine echocardiography and superior to it in
those with poor acoustic windows.

DE-MRI has been found to be comparable to each
of DSE,SPECT, and PET in several studies. However,
DE-MRI is superior to DSE for viability determination
in patients with poor endocardial border definition
and in patients with atrial fibrillation . Moreover, com-
bination of different CMR parameters ( a nonviability
test delayed gadolinium enhancements and a viabili-
ty test( inotropic stimulation with dobutamine) seems
to be the optimal combination to assess hibernating
myocardium.

ii) LGE or dobutamine stress CMR Vs Resting Tl-201 or Tc 99m sestamibi & PET F-18 FDG F-18 FDG PET MYOCARDIAL VIABILITY :
or Stress Rb-82 or N-13 Ammonia radiotracers in the assessment of myocardial viability.
A fundamental characteristic of the myocardium is
its continuous requirement for oxygen & metabolic
substrates to meet its energy demands. This pro-
cess largely occurs by oxidizing fatty acids & glu-
cose. Under normal conditions, fatty acids are the
preferred energy source for overall oxidative me-
tabolism. When blood flow is reduced to the heart
muscle & ischemia ensues, fatty acids can no longer
be oxidized & glucose becomes the preferred energy
source. This metabolic phenomenon is useful for the
identification of myocardium that is underperfused

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Cardio Diabetes Medicine 2017 373

but still viable. Such tissue is often hypokinetic or aki- mic insulin clamp technique.
netic but returns to normal or near-normal function if
blood flow is restored. Consequently, in patients with Under fasting conditions the normal myo-
severely impaired ventricular function, combined with cardium primarily utilises fatty acids, while glucose
measurements of myocardial perfusion & glucose utilisation and thus FDG uptake becomes minimal.
metabolism have been advocated. It may be note- Under this condition, ischaemic myocardium with en-
worthy to mention that eating fat & protein shifts the hanced glucose metabolism markedly takes up FDG,
heart away from using glucose as an energy source. which is displayed on PET images as hot spots. The
problem of imaging under fasting conditions is the
Metabolic tracers. heterogeneous distribution of FDG in to normal myo-
cardium. Usually the lateral wall of the left ventricle
Fluorine-18 FDG, C-11 palmitate, & C-11 acetate are tends to show higher FDG uptake than the septum.
typical examples of PET radiopharmaceuticals used High background activity with low tissue FDG uptake
for metabolic cardiac studies. ‘Deoxyglucose’ is an also leads to poor image quality. For these reasons
analog of glucose that can be labeled with F-18, a FDG PET under fasting condition, the interpretation
cyclotron produced radionuclide, to form F18-FDG. Its showed carefully be done for clinical viability assess-
myocardial uptake reflects overall myocardial utiliza- ment.
tion of glucose. Palmitate is a naturally occurring fat-
ty acid that can be chemically synthesized & labeled The most commonly used protocol is oral glucose
with C-11, a cyclotron-produced radionuclide with a loading. Ingestion of about 50-70g of glucose stim-
physical half-life of approximately 20.4 minutes. Its ulates insulin secretion & increases the FDG uptake
myocardial uptake & clearance reflect the myocardial into normal myocardium to near maximum. This en-
utilization of fatty acids. hances the image quality with homogenous myocar-
dial FDG uptake. Euglycaemic insulin clamping is an
Fluorine-18 FDG metabolic Imaging alternative technique to oral glucose loading and is
slightly more complex but guarantees more stable
18F- FDG is a glucose analogue which crosses the & controlled metabolic conditions. FDG uptake in to
capillary and sarcolemmal membrane at a rate pro- normal & ischaemic but viable myocardium is en-
portional to that of glucose. Following myocardial hanced and negative FDG uptake is considered to
uptake, FDG is phosphorylated to FDG phosphate indicate scar tissue.
and is then trapped in the myocardium unlike phos-
phorylated glucose. Regional myocardial uptake of Thus hibernating myocardium therefore would
FDG therefore reflects relative distribution of region- demonstrate increased FDG uptake in the fasting
al rates of exogenous glucose utilization, unlike the state unlike the surrounding normal myocardium. But
brain which mainly depends upon glucose metabo- in the post prandial state (with oral glucose loading)
lism. The myocardium is an omnivore. There are three hibernating myocardium would demonstrate FDG up-
major circulating substances which affect the myo- take. Therefore either preserved or even enhanced
cardial metabolism: blood glucose, FFAs and insulin. FDG uptake in dysfunctional myocardial regions rep-
Many other factors, such as the fasting period & age, resent presence of myocardial viability by the help of
also affect the FDG uptake. Even hospitalization sta- most popular criterion of flow-metabolism mismatch
tus (in patient or out patient) has an influence on the methods. However using this criterion requires a per-
myocardial FDG uptake . fusion image preferably acquired either with PET or
SPECT perfusion study.
This complexity interferes with the interpretation of
data obtained from FDG-PET imaging. To accommo- Regional dysfunction due to stunned myocardium
date this complexity of metabolism there are several may be manifested by normal blood flow & normal,
different protocols for myocardial FDG PET imaging. enhanced or reduced glucose utilization using FDG
These protocols can be divided into two major cat- & flow images. Only criteria to diagnose this myo-
egories. cardium is the presence of regional myocardial wall
motion abnormalities.
I) One is imaging under low myocardial glucose
metabolism which includes imaging under fasting
conditions.

II) The other protocol images the myocardium under
high to maximum myocardial glucose metabolism
which includes oral glucose loading & the euglyce-

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374 Cardiac MRI vs PET Scan

Perfusion-metabolism mismatch using N-13 ammonia & F-18-FDG PET imaging tracer
suggesting decreased perfusion with adequate metabolism in the involving intero- septal
and apical. Myocardium in the lower row images as compared to match defect involving

anterior segment seen in the upper images.

Clinical uses of cardiac MRI Vs PET scan in
infiltrative cardiac disease :

Resting myocardial perfusion image shows multiple defects in antero-septal and apical Cardiac MRI Vs PET scan in sarcoidosis ,
myocardial segment(Ist row of images.) without any evidence of hibernating myocardium Amyloidosis :
in the form of match defects on FDG images(2nd row)
The high spatial resolution and soft tissue character-
Resting myocardial perfusion image shows multiple perfusion defects seen in anteri- ization of cardiac MRI imaging has shown a great po-
or,septal and apical myocardial segments (1st row of images),which shows significant tential in the identification & evaluation of myocardial
evidence of hibernating myocardium involving anterior and apical myocardial segments alteration related to inflammatory cardiomyopathies
in the form of mismatch defects without any evidence of hibernating myocardium in such as sarcoidosis . Sarcoidosis is a granulomatous
septal segment in the form of match defect(scarred myocardium disease of unknown etiology that most commonly
affects the lungs and mediastinal lymphnodes with
cardiac involvement responsible for 30% to 85% of
deaths from an atrio -ventricular conduction block
or ventricular arrhythmia related to granulomatous in
filtration or subsequent fibrotic scars. The diagnosis
of cardiac sarcoidosis is often confirmed invasively
by endomyocardial biopsy performed through right
heart catheterization. Since cardiac involvement is
homogeneous, the histologic confirmatory diagnos-
tic & procedural risk are related to the number & lo-
cation of samples and there is a high prevalence of
negative findings. An accurate noninvasive imaging
technique is therefore necessary to exclude cardiac
involvement or to help guide biopsy in segments
with suspected infiltration. Cardiac MR imaging has
emerged as the current modality of choice for the
diagnosis of cardiac involvement; with regional func-
tional assessments T2 weighted sequences for the
detection of oedema & inflammation complementing
the LGE sequences for the identification of fibrotic
tissue. The value of F-18 FDG PET studies for identify-
ing cardiac sarcoidosis & correlative studies of CMR &
PET showed comparable accuracy of both modalities
in detecting myocardial lesion with better correlation
of abnormal PET findings. But preparation before PET
study is very much crucial to have optimal images
such as extended fasting, a low protein, high fat diet
or heparin infusion. However simultaneous PET / MR
imaging in patients with suspected cardiac sarcoid-
osis benefits from the improved spatial resolution
of LGE sequences to describe areas of myocardial
infiltration that can be further characterized by their
metabolic activity on PET images as inflammatory
or scar related, complimenting the less specific MR
sequences. Additionally PET also provides a more
comprehensive whole body assessment of extra car-
diac involvement including pulmonary or neurologic
extension of the disease that are less accessible by
MR imaging alone.

GCDC 2017

Cardio Diabetes Medicine 2017 375

PET MR in active cardiac sarcoidosis 3D LGE with F-18 labelled fluoro- deoxyglucose Conclusion :
(F-18 FDG) PET suggestive of active inflammation surrounding requires of established
scar white arrows indicate regions of established scar by LGE imaging . Last rows shows Hybrid PET/MR imaging could also become the
increased row of FDG tracer uptake entrance rows around the scar areas with & small imaging modality of choice for the evaluation and
spleen rows increased FDG tracer uptake. follow-up of new therapeutic techniques aimed at
tissue regeneration and myocardial repair. Recent
Cardiac MRI Vs PET Scan in the evolution & studies have shown that PET imaging can be used
characterization of atheramatous plaque : for assessment of the kinetics of stem cell therapy
in myocardial infarction. Dual labeling of stem cells
The ability to acquire high definition MR images with with iron particles may offer new tools for monitor-
tissue characterization and functional capability com- ing the deliver, survival, and migration of cells after
bined with metabolic information provided by current cell transplantation. However, the specificity of MR
& future PET tracers opens new perspectives in the imaging and PET signals still needs to be validated
clinical application of PET/MR imaging beyond the in order to be applicable in cell therapy; therefore,
assessment of coronary artery disease. One of the hybrid PET/MR imaging is expected to play a major
most promising applications is the evaluation and role in the validation process, allowing longitudinal
characterization of atheramatous plaques in coro- studies that provide combined structural and biologic
nary & peripheral vassals. The ability to detect high information.
risk vascular plaques even in the absence of signif-
icant luminal obstruction could leap identify those The integration of PET and MR imaging modalities in
plaques that could potentially rupture and cause a single device will certainly open new perspectives
future vascular events. The causes of plaque insta- in cardiac imaging by bringing together the two most
bility & high rupture risk are believed to be related advanced imaging technologies that provide compet-
to inflammatory processes and the accumulation of ing but complementary information. Although MR im-
macrophages in the lipid core of vessel plaques. Al- aging continues to expand in cardiology, becoming
though inflammation can be detected with F-18 FDG increasingly adopted in a clinical routine, the addi-
PET, more specific tracers are also being explored tional metabolic & functional information provided
such as F-18 – galacto –RGD which binds to Lv B3 in- by PET tracers can provide valuable complementary
tegrin, a cell surface glycoprotein receptor, F-18 la- data for specific subsets of patients who will bene-
belled NaF(sodium fluoride) relating to metabolically fit from the added diagnostic accuracy of PET. The
active calcific plaques are still have to make their first generation of coplanar PET/MR imaging devices
way in to clinical use, several studies have to report- that combined separate PET and MR imaging scan-
ed the use of F-18 FDG PET imaging as a means of ners led the way to new imaging protocols for the
characterizing inflammatory activity in atherosclerotic evaluation of myocardial viability and inflammatory
plaque and thus as a surrogate biomarker for detect- cardiomyopathies . The more recent generation of in-
ing vulnerable plaques. tegrated devices that allow the simultaneous acquisi-
tion of PET & MR images can provide the additional

Cardio Diabetes Medicine

376 Cardiac MRI vs PET Scan

perspective of acquiring both modalities simultane- RGD peptides for imaging and therapy . Eur J Nucl Med Mol Imag-
ously after physiologic interventions such as phar- ing.2012;39(suppl 1): S 126-S 138.
macologic stress. Integrated devices should allow
the performance of rest and stress imaging proto- 13. Dweck MR,Chow MW, Joshi NV, et al. Coronary arterial 18F-sodium fluoride
cols for the exploration of stress-induced ischemia in uptake : a novel marker of plaque biology. J Am Coll Cardiol. 2012;59:
CAD, showing both functional & biologic alterations 1539-1548.
in myocardial function. Early reports have shown the
feasibility of combined PET/MR imaging protocols for 14. Cocker MS, McArdle B, Spence JD, et al. Imaging atherosclerosis with
the detection of CAD. The upcoming new generation hybrid [18 F] fluorodeoxyglucose positron emission tomography /computed
of 18F- labeled flow tracers will bring additional sup- tomography imaging: what Leonardo da Vinci could not see. J Nucl Car-
port for new PET applications in clinical practice in diol.2012;19:1211-1225.
centers that do not benefit from a local cyclotron.

Further development of new tracers will expand the
range of clinical capabilities of PET/MR imaging in
cardiology, allowing more specific evaluation of vas-
cular atherosclerosis and cardiomyopathy and the
monitoring of new therapeutic tools for myocardial
remodeling after acute ischemic events.

References :

1. Schwitter J, Wacker CM, van Rssum AC, et al. MR-IMPACT: comparison
of perfusion-cardiac magnetic resonance with single –photon emission
computed tomography for the detection of coronary artery disease in a
multicentre, multivendor,randomized trial. Eur Heart J. 2008;29: 480-489.

2. Rischpler C, Nekolla SG, Dregely I, Schwaiger M. Hybrid PET/MR imaging
of the heart: potential, initial experiences, and future prospects. J Nucl
Med.2013;54 :402-415.

3. Ratib O, Nkoulou R, Schwaiger M. PET/MR : a new era in multimodality
molecular imaging. Clin Transt Imaging. 2013;1:10.

4. Ibrahim T, Nekolla SG, Schreiber K,et al. Assessment of coronary flow
reserve: comparison between contrast-enhanced magnetic resonance
imaging and positron emission tomography. J Am Coll Cardiol. 2002;39:
864-870.

5. Fiechter M. Ghadri JR, Gebhard C, et al. Diagnostic value of 13N-ammonia
myocardial perfusion PET : added value of myocardial flow reserve. J. Nucl
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6. Beanlands RS,Nichol G,Huszti E, et al. F-18- fluorodeoxyglucose positron
emission tomography imaging-assisted management of patients with severe
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7. Schinkel AF, Poldeermans D, Elhendy A, Bax JJ. Assessment of myocardial
viability in patients with heart failure. J Nucl Med.2007;48:1135-1146.

8. Eisentopf J, Achenbach S, Ulzheimer S, et al. Low-dose dual-source CT
angiography with iterative reconstruction for coronary artery stent evalu-
ation. JACC Cardiovasc Imaging.2013; 6:458-465.

9. Takeda N, Yokoyama I, Hiroi Y, et al. Positron emission tomography predi-
cated recovery of complete A-V nodal dysfunction in a patient with cardiac
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10. Stone GW, Maehara A, Lansky AJ, et al. A prospective natural- history
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11. Laitinen I, Saraste A, Weidl E, et al. Evaluation of alphavbeta3 inte-
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12. Gaertner FC, Kessler H, Wester HJ, Schwaiger M, Beer AJ. Radiolabelled

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Cardio Diabetes Medicine 2017 377

Mechanical Circulatory Support for
Advanced Heart Failure

Dr. Liviu Klein MD, MS

Director, Mechanical Circulatory Support and Heart Failure Device Programs,
University of California San Francisco, San Francisco, CA, USA

Abstract: survival in this population. As result, the number of
recipients bridged to transplant with ventricular as-
Due to the marked increase in the number of ad- sist devices has increased dramatically over the last
vanced (end stage) heart failure patients and the lack decade; in 2016, 51% of adult recipients in the United
of suitable donors to allow heart transplantation, the States were bridged with ventricular assist devices,
majority of these patients do not survive. Recent im- compared to only 19% in 2000.
provements in technology have allowed development
of durable ventricular assist devices that can support The clinical profile of the advanced heart failure pa-
an increasing number of patients for longer duration tients includes several of the following characteristics
of time while allowing restoration of fairly normal despite optimal medical and electrical therapies: (1)
quality of life. Over the past decade better patient severe symptoms with New York Heart Association
selection has resulted in improved outcomes, with 3- (NYHA) functional class IIIor IV, continuously for at
and 5-year survival approaching survival after heart least 2 months; (2) severe impairment of functional
transplantation in individuals older than 60 years of capacity demonstrated by either inability to exercise,
age. Better understanding of the relation between se- a 6-min walk distance below300 m, or a peak oxygen
verity of patient condition at the time of implant and consumption below 12-14 ml/kg/min; (3) recurrent ep-
outcomes has resulted in an increasing number of isodes of hospitalization with signs of fluid retention
patients in cardiogenic shock being supported with and/or peripheral hypoperfusion;(4) left ventricular
temporary mechanical circulatory support to allow for ejection fraction below 25-30%; (5) high left or right
restoration of multi organ function ventricular filling pressures with low cardiac output at
cardiac catheterization;and (6) evidence of systemic
before the implantation of durable ventricular assist organ injury, in particular renal and hepatic dysfunc-
devices. tions (elevated blood urea nitrogen, creatinine and
bilirubin levels). Two or more of these findings should
Manuscript: prompt referral to a specialized heart failure program
for considerationof advanced therapies.
Introduction
In order to further refine the prognosis and the risk
Heart failure incidence and prevalence are increasing of surgical intervention in advanced heart failure pa-
worldwide at staggering levels. Close to 40% of the tients, the Interagency Registry for Mechanically As-
heart failure patients have heart failure with reduced sisted Circulatory Support (INTERMACS) scale assigns
ejection fraction, and 10% of these patients have patients into seven levels according to their hemody-
advanced (end stage) disease,yielding an estimated namic profile and functional capacity (Table 1). Based
cohort of several hundred thousands patients world- on this risk profile, the time frame for intervention
wide who have a high one-year mortality (over 30%) should be within hours (profile 1) ordays (profile 2), or
and can benefit of advanced therapies such as heart more elective such as weeks to months (profiles 3-6).
transplantation or ventricular assist devices.The num- During the first decade of modern circulatory sup-
ber of heart transplants performed worldwide is lim- port (2000-2010) the majority of patients implanted
ited to 5-6,000 due to donor availability highlighting with durable ventricular assist devices were profiles 1
the need for mechanical alternatives for improving

Cardio Diabetes Medicine