Non-Invasive physiological assessment of coronary circulatory function

Non-Invasive physiological assessment of coronary
circulatory function
Presenter
Dr Praveen Gupta
Moderator
Dr Santhosh Satheesh
JIPMER
Pondicherry
India
04.01.2018
1

Introduction
 Classification of CAD into one, two, and three vessels simple and not free of limitations
 Plotnick remarked decisions based on the number of vessels is unidimensional approach to a
multidimensional problem, and demanded less anatomy and more physiologyin IHD
 Topol and Nissen warned in 1995 of the excessive concern of cardiologists for coronary
luminology
2
Candell-Riera J, Martín-Comín J, Escaned J, Peteiro J. Physiologic evaluation of coronary circulation. Role of
invasive and noninvasive techniques. Revista Española de Cardiología. 2002 Mar 1;55(03):271-91.

Noninvasive Methods For The Physiological
Assessment Of Coronary Circulation
 PET
 SPECT: Single-photon emission computed tomography
 Stress Echocardiography
 Contrast echocardiography
 Cardiac MRI
 CT
 PET-CT
 Electrocardiographic exercise stress test
3

PET
 Combines high spatial resolution (down to secondary or tertiary coronary branches) with
quantitative measures of rest and stress myocardial perfusion in absolute units to compute
absolute CFR
 Quantitative measures correlated with low-flow thresholds causing ischemia.
 Only noninvasive technique that allows quantitative assessment
 Uses isotopes with a very short mean life (min/s)
 High energy (511 KeV)
 Tissue attenuation is minimal
 Isotopes used are 13N-ammonium & 82Rb
4

PET
 Highly complex
 Expensive
 Use is strictly limited
6

SPECT
 Use for assessment of myocardial perfusion in clinical practice
 Using thallium chloride (201TlCl) as the radiomarker
 Thallium-201 is a monovalent cation of behavior similar to potassium
 Penetrates the cell by active uptake (Na pump) and passive diffusion
 Myocardial uptake is proportional to coronary flow and peaks at approximately20 min.
7

SPECT
 Once peak value is reached, redistribution
takes place, by which intra and
extracellular concentrations balance &
201Tl circulates from high-uptake to low-
uptake zones.
 Post-stress study must be acquired quickly
(within 10 min of radiomarker
administration) and before redistribution
begins
8

Other agent for SPECT
 Despite the excellent myocardial extraction and flow kinetic properties of 201Tl, its energy spectrum
of 80 keV is suboptimal for conventional gamma cameras (ideal photopeak in the 140-keV range).
 In addition, the long physical half-life of 201Tl (73 hours) limits the amount of 201Tl that may be
administered to stay within acceptable radiation exposure parameters.
 99mTc-labeled tracers improve on these two limitations of 201Tl.
 Although three 99mTc-labeled tracers—sestamibi, teboroxime, and tetrofosmin—have received U.S.
Food and Drug Administration (FDA) approval for detection of CAD, only sestamibi and
tetrofosmin are available for clinical use at present
 Penetrate the cell by passive diffusion
 No redistribution.
 Administered in two doses ( stress study and at rest study)
 99mTc emits 140 keV of photon energy and has a physical half-life of 6 hours
9

SPECT
 Effort stress test using a treadmill or bicycle, or pharmacological stress: dipyridamole,
adenosine and dobutamine
 In health, images, post-stress or at rest shows homogeneous activity in the LV myocardium
 Any zone of hypoactivity must be considered pathological
 Sensitivity and specificity 90-95%
10

11
Figure 3. Cardiac perfusion SPECT study at stress (first and third rows) and rest (second and forth rows) shows
reversible perfusion defect in the anterolateral wall (arrows) consistent with myocardial ischemia. The perfusion
study has been corrected for attenuation by using maps computed from low-dose CT scans. The color convention
used shows normal perfusion in brighter colors and decreased perfusion in darker colors.

Diagnosis of multivessel disease
 Reversible perfusion defects in more than one coronary region
 Transitory ischemic left ventricular dilation and
 Post-effort pulmonary radionuclide uptake
12

Gated-SPECT
 Synchronizing onset of R-wave in the
ECG and dividing cardiac cycle into 8 or
16 segments
 Simultaneous assessment of coronary
perfusion and cardiac function
 Helps to differentiate defects due to
artifacts from those due to ischemia, as
well as the myocardial contractile reserve
by means of low-dose dobutamine
stimulation. 13

Role of SPECT
 Very useful in patients with chronic coronary arterial disease
 Cases in which the significance of a certain coronary stenosis is inconclusive it is useful
 Correlates well with CFVR, relative CFVR, FFR, and diastolic FFR
 In 85% of cases coincides with the severity of the disease and in decision making
 For the diagnosis of the culprit lesion is approximately 84%
 RCA (91%) ,LAD (79%) LCX (62%)
14

Limitation
 Does not allow absolute quantification of the coronary flow,
 Tell only about the most hypoperfused region with respect to the least hypoperfused
 Non-atherosclerotic causes that can give rise to perfusion defects: the X syndrome, coronary
spasm, coronary ectasia, coronary fistula, and hypertrophic cardiomyopathies
15

Discordant cases
 Ischemia to the territory of the right coronary or circumflex
 Three-vessel disease with stenosis of similar severity
 Totally occluded artery
16

Echocardiography for the diagnosis of myocardial ischemia
 Very sensitive for the diagnosis of acute ischemia
 For the diagnosis of myocardial viability
 Low cost, Broad availability, absence of radiation, and can see any valve dysfunction
 Main limitation, difficulty of making a quantitative analysis
 New techniques like Doppler tissue studies strain and M-mode help in quantitative analysis
 Broad interobserver variability
17

Concept of stress ECHO
 Concept of the ischemic cascade
 In the presence of ischemia, in first place disturbances in myocardial perfusion occur
 Then, disturbances in diastolic function appear
 Eventually, disturbances in systolic function
 Finally, ECG disturbances and angina appear
18

Stress echocardiography
 Exercise, dobutamine, &electrical stimulation increase myocardial oxygen demand
 Bicycle and treadmill techniques used successfully, safe and well tolerated
 Bicycle advantage to image throughout exercise
 Bicycle technique more sensitive, whereas treadmill exercise more specific
 Vasodilator drugs like dipyridamole and adenosine produce ischemia by coronary
theft mechanisms
19

Concept of pharmacological stress ECHO
23

Interpretation of stress echocardiography
 Analyzed based on a subjective assessment of regional wall motion
 Comparing wall thickening and endocardial excursion at baseline and during stress
 The rest or baseline echocardiogram is first examined for the presence of global systolic
dysfunction or regional wall motion abnormalities
 Normal response is hyperdynamic wall motion
25

Interpretation of stress echocardiography
 Normal response to stress includes decrease in end-systolic and end-diastolic volume
 Lack of hyperkinesis is abnormal and caused by myocardial ischemia
 Failure of the end-systolic size to decrease is an abnormal response
 Increase in volume with stress indicates severe and extensive (i.e., multivessel) disease
26

Stress ECHO
 Sensitivity of 80% and specificity of 85-90%, close to that of radionuclide studies
 Limitations are the need for special training, inability to walk and failure to attain an adequate
tachycardia
27

Assessment of the coronary reserve
 Coronary reserve represents the capacity of the coronary arteriolar bed to dilate in response to
increased cardiac metabolic needs.
 It is calculated as the ratio between the velocity of coronary flow after the administration of a
vasodilator (usually adenosine or dipyridamole) and in baseline circumstances
 Coronary reserve decreases progressively when a fixed lesion produces a stenosis of 50%, in
such a way that it is completely suppressed with lesions of more than 90%
28

 TEE allows the visualization of the proximal segments of coronary arteries and through the
distal portion of the anterior descending artery
 Allowing the coronary reserve to be calculated at that level
 Distal coronary reserve is excellent because the reserve calculated reflects the residual
vasodilator capacity of the vascular bed, which is affected specifically by proximal lesions of
the proximal and middle anterior descending coronary
29

 Sensitivity of 91% and specificity of 76% for detecting stenosis >75%.
 Flow signal was optimal without contrast in 55% and in all after contrast was administered
 Reduced in left ventricular hypertrophy, small-vessel disease, constrictive
pericarditis,cardiomyopathies,transplanted hearts, and left bundle-branch block
30

Myocardia perfusion echocardiography
 Used With vasodilators
 Detection of ischemia by revealing a
heterogeneous flow
 Contrast agents used intravenously
 Contrast agents produce bubbles that enter
the coronary circulation and expand and
compress when exposed to ultrasound.
31

Myocardial perfusion echocardiography
 Detection of bubbles depends on capacity to generate two resonance waves of different
frequency, in contrast with myocardial tissue
 Ultrasound destroys the bubbles, if mechanical index is high
 The bubbles can be destroyed by the fleeting emission of ultrasounds, but in the meantime
new bubbles that can be detected enter the system
 Numerous problems mainly to artifacts
32

Myocardial contrast-enhanced echocardiography: schematic demonstrating the approach to myocardial perfusion imaging during steady-state infusion
of a contrast agent. A high–mechanical index impulse (MI) destroys all the intramyocardial bubbles to yield an unenhanced image that will serve as the reference
baseline. Subsequently, bubbles will return to and progressively enhance the myocardium until a steady-state concentration is reached. This may be monitored by
either a triggered approach in which imaging is performed on end-systolic images at increasing numbers of beats after the flash (1, 2, 3, 4, etc.) or by using low–
mechanical index continuous imaging. Enhancement will increase until a steady-state level is achieved (in this hypothetic example at a five-beat pulsing interval or
after 4 seconds of low-MI imaging). The rate at which replenishment occurs and the degree of enhancement under steady-state conditions, as can be quantitated
by video intensity, reflect myocardial perfusion. LV = left ventricle; RV = right ventricle. (Modified from Wei K, Jayaweera AR, Firoozan S, et al: Quantification of
myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 97:473, 1998.) 33

 Agreement between techniques was greater in the territory of the anterior descending artery
and right coronary , and significantly smaller in the territory of the circumflex artery
 This is due to the large number of false defects obtained with echocontrast on the lateral face.
 In effect, due to the angle of incidence of ultrasound on the lateral wall, false defects may be
more common in this territory.
34

 Good sensitivity 80-95%, lower specificity (50-75%)
 Can also evaluate the non-reflow phenomenon
35

Cardiac MRI
 CMR perfusion imaging examines the first-pass transit of an intravenous bolus of GBCA
 Uses Fast bright blood gradient-echo in MRI during the injection of GBCA bolus
 Gadolinium provides strong signal enhancement in well-perfused regions, compared with
hypoenhancement (dark regions) in poorly perfused myocardium
 Provide information of blood flow at the endocardial/ epicardial or at a segmental level
36
Bonow RO, Mann DL, Zipes DP, Libby P. Braunwald's Heart Disease: A Textbook of Cardiovascular
Medicine. Elsevier Health Sciences; 2015.

CMR imaging of ischemia and infarct extent in a 59-year-old obese man with dyspnea on exertion. A, First-pass
resting perfusion image reveals a severe defect in the inferolateral wall (arrow). B, Late gadolinium enhancement
demonstrates two foci of previously unrecognized infarcted myocardium (arrows). Subsequent coronary angiography
revealed severe stenoses in the left circumflex and right coronary arteries. Images of ischemia and infarction can be
superimposed and compared qualitatively and quantitatively.
37

Typical pattern of microvascular obstruction in a patient with ST-elevation myocardial infarction
due to an occluded left anterior descending artery, treated with primary percutanous coronary
intervention (A) Demonstrates first pass perfusion images with hypoperfusion of the
anteroseptum, especially at day 2 and week 1 postmyocardial infarction. (B) Demonstrates late
gadolinium-enhanced images with the dark signal at the subendocardium at each time point
representing regions of microvascular obstruction.
38

Cardiac MPI
 Pharmacologic stress CMR myocardial perfusion imaging (MPI) for used in CAD
 Combined perfusion, LGE, and cine CMR data yield the highest sensitivity and specificity
 Not limited by attenuation artifacts
 Free from ionizing radiation
 Three- to four-fold higher spatial resolution than SPECT
 Sensitivity 91% & specificity of 94% for functionally significant stenosis defined by FFR
39

Vasodilator stress cardiac MRI protocol
40

Qualitative interpretation of cardiac MRI perfusion imaging.Top row shows adenosine stress images, while
the bottom row shows rest images. Left column: basal left ventricle; middle column: mid left ventricle; right
column: apical left ventricle. The white arrows point to a large perfusion defect in the anterolateral, infero-
lateral, inferior and infero-septal wall, extending from the basal to the apical slice. 41

Cardiac MRI
 A stress CMR study takes 35 to 45 minutes (compared with 2 hours for SPECT)
 CMR MPI also can characterize the dynamic range of myocardial blood flow without being
limited by plateau effect of counts at high flow rates as seen in some nuclear tracers
 CMR MPI performed better than SPECT in detecting coronary stenosis especially in the
group of Patient with multivessel stenosis
42

Cardiac MRI
 Negative CMR MPI have annualized cardiac event rates of less than 1%.
 CMR MPI provide effective risk assessment in women
 CMR often provides clinicians with alternative diagnoses in patients suspected to have CAD
 CMR MPI can be analyzed quantitatively using the signal intensity versus time curves
measured from myocardial segments.
 Common semiquantitative parameters include signal upslope (rate of rise of the ascending
curve), upslope integral (area under the upslope), and contrast enhancement ratio (ratio of
peak to baseline signal intensity).
43

Cardiac MRI
 Fully quantitative analysis of CMR perfusion yields absolute myocardial blood flow (in
milliliters per minute per gram of tissue) using deconvolution methods and modeled
compartmental analysis.
 Quantitative analyses have potential advantages including minimization of reader’s bias and
enhanced detection of abnormality in cases of balanced perfusion reduction or inadequate
vasodilation
44

Dobutamine Stress Cardiac MRI
 Excellent sensitivity (83% to 86%) and specificity (83% to 86%)
 Provides strong prognostic value in risk assessment of patients
 Addition of stress myocardial perfusion and myocardial strain encoding during dobutamine
stress can be a helpful adjunct to cine CMR in detecting myocardial ischemia
 Accelerated real-time cine CMR imaging, eliminates breath-holding or ECG gating during
dobutamine stress testing, yielded encouraging results
 Treadmill exercise CMR is investigational currently but has been shown to be feasible in
highly experienced centers
45

46
Figure 3
Three examples of CMR, SPECT, and angiographic findings
(A) Stress perfusion CMR shows inducible hypoperfusion (ischaemia) in the septum and anterior wall (arrow shows dark area of hypoperfusion), SPECT is concordant (arrows show lower signal
counts during stress), indicating anteroseptal inducible ischaemia, and angiography confirms a stenosis (arrow) in the left anterior descending artery. (B) Late gadolinium-enhanced CMR (arrow
shows hyperenhancement in the inferior wall) and SPECT (fixed defect; arrows show comparable inferior defect at rest and stress) are concordant, showing a transmural inferior myocardial
infarct with the corresponding right coronary artery chronic total occlusion (arrow) seen at angiography. (C) Late gadolinium-enhanced CMR shows subendocardial inferior infarction (arrow),
SPECT was reported as normal (no wall motion abnormality), and the angiogram shows coronary atheroma but no clinically significant stenosis (or occlusion). As per study protocol, CMR in this
patient was classified as a false positive, showing the potential limitations of angiography as a reference test for the detection of coronary heart disease. The case also shows that SPECT can miss
small subendocardial infarcts. CMR=cardiovascular magnetic resonance. SPECT=single-photon emission computed tomography
Greenwood JP, Maredia N, Younger JF, Brown JM, Nixon J, Everett CC, Bijsterveld P, Ridgway JP, Radjenovic A, Dickinson CJ, Ball SG. Cardiovascular magnetic resonance and single-photon
emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial. The Lancet. 2012 Feb 10;379(9814):453-60.

Cardiac Computed Tomography
 Myocardial attenuation reflects relative coronary blood flow on first pass imaging
 First-pass CT stress perfusion imaging is being developed
 Imaging protocol includes contrast-enhanced CT angiography both at rest and during the
administration of adenosine agonists
 Most commonly using 320-slice CT or 128-slice dual-source CT
 Sensitivity 72% to 98%, and specificity 71% to 92%
 Primary limitation radiation exposure
47

Cardiac computed Tomography
 Computational FFR from resting coronary CT angiographic images
 Measured from standard first-pass coronary CT angiography
 Overall accuracy was limited at 73%, with sensitivity of 90% and specificity of 54%.
 Advantage of assessment from routine coronary CT angiograms acquired at rest
48

CT fractional flow reserve (FFR) using computational fluid dynamics. From the invasive coronary angiogram (A), coronary
lesions assessed by invasive FFR (B) are correlated with CT-derived FFR (C). (From Nakazato R, Park HB, Berman DS, et al:
Non-invasive fractional flow reserve derived from CT angiography (FFRCT) for coronary lesions of intermediate stenosis
severity: Results from the DeFACTO study. Circ Cardiovasc Imaging 6:881, 2013.)
49

Conclusions
 Non invasive assessment has important role
 Do not treat stenosis
 Treat both stenosis and physiology
 Cardiac MRI and PET-CT are new imaging modality
 Use Stress ECHO as much as possible
 We first done MBBS then MD then DM so similarly we are family physician then
general physician and then interventional cardiologist
 Intervention has a role but use it very judiciously because it has its long term
complication and cost
52

Non-Invasive physiological assessment of coronary circulatory function

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