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Cookbook_perf_r811.pdfA Guide to Myocardial Perfusion Analysis During Adenosine Mediated Coronary Vasodilatation for Assessment of Myocardial Dipyridamole is the prodrug of adenosine and is activated by metabolism in the liver. Thus, vasodilatory capacity depends on Magnetic resonance perfusion imaging has individual metabolism rate, usually resulting in a longer half-life, prolonged side effects studies and first larger patient trials. In perfusion deficits is a very sensitive indicator of ischemia in the presence of significant coronary artery stenoses. Most Both, normal and stenotic coronary arteries are dilated to their maximum using these perfusion defects only occur during stress, such as pharmacological vasodilation. This can be optimally achieved using adenosine or dipyridamole as pharmacological stress maximally dilated at rest (to allow maximal blood flow and compensate for the stenosis) agents, both of which proved to be safe and and cannot be dilated any further. Thus, vasodilation with dipyridamole or adenosine induces an increase of blood flow in Techniques currently used in clinical routine coronary arteries ("coronary steal"), disadvantage of radiation and low spatial resolution, which prohibits the assessment found in areas supplied by stenotic coronary of subendocardial ischemia. This cookbook arteries. With adenosine a maximal coronary provides instructions for the application and vasodilation can be achieved safely with an with cardiac magnetic resonance imaging. The vasodilatory effect of adenosine may The methodology has been developed for a result in a mild-to-moderate reduction in systolic, diastolic and mean arterial blood pressure (< 10 mmHg) with a reflex increase a 30 mT Master gradient system (slew rate: in heart rate. Most patients complain about anginal chest pain. These effects, however, synergy coil. Software: Release 8.1.1 and are transient and usually do not require Since adenosine exerts a direct depressant first-, second- and third-degree AV block and sinus bradycardia have been reported in 2.9%, 2.6% and 0.8% of patients. Also, baroreceptor reflex are able to maintain blood pressure in response to adenosine by increasing cardiac output and heart rate. Adenosine can also cause a paradoxical increase in systolic and diastolic blood pressure, which mostly develops in individuals with significant left ventricular hypertrophy. These increases are transient Adenosine, an endogenous nucleotide, is a potent vasodilator of most vascular beds, except for hepatic and renal arterioles. It primarily through activation of carotid body exerts its pharmacological effect through chemoreceptors, intravenous administration surface adenosine receptors. The essence of reduction in arterial PCO2 and respiratory the pharmacological mechanism lies in the alkalosis. Approximately 14% of patients inhibition of the slow inward Ca2+ current, complain of dyspnea and an urge to breathe thereby reducing calcium uptake, and in the activation of adenylate cyclase through A2 receptors in smooth muscle cells. German Heart Institute Berlin & cmr-academy.com Adenosine should be used with caution in bundle branch block and should be avoided intravenous adenosine infusions in different in patients with high-grade AV block or sinus diagnostic modalities of cardiac imaging. node dysfunction. Adenosine should be used with caution if a patient is receiving any So far, there is evidence accumulated in medications that already depress the sinus over 10,500 patients studied in thallium node and/or AV node (e.g. beta-blockers, presents a safe method of acquiring stress imaging data. Adenosine should be discontinued in patients who develop persistent or symptomatic high-grade block or significant drop in systolic blood pressure (>20 mmHg). radionuclide imaging of 9,256 consecutive The drug should be discontinued in case of completed in 80% of patients, required dose reduction in 13% and was terminated early Also, adenosine should be used with caution in 7%. Interpretable imaging studies were obtained in 98.7% of patients, and 0.8% of stenotic valvular heart disease, pericarditis patients received aminophylline. Minor and and pericardial effusion, stenotic carotid well tolerated side effects were reported in artery disease, cerebrovascular insufficiency 81.1% of patients. There were no deaths, one myocardial infarction, seven episodes of severe bronchospasm and one episode of Adenosine infusion should be exercised with pulmonary edema. Transient AV node block caution in patients with obstructive lung occurred in 706 patients (first-degree in 256, second-degree in 378 and third-degree constriction (emphysema, bronchitis, etc), in 72) and resolved spontaneously in most patients (n = 508) without alteration in the bronchoconstriction or bronchospasm (e.g. adenosine infusion. There were no sustained respiratory difficulties, adenosine should be immediately discontinued. Table 1: Dipyridamole / Adenosine stress protocol No caffeine (tea, coffee, 0.56 mg/kg/min for 4 Aminophylline 250 mg chocolate, etc.) or minutes, maximal effect i.v. slowly injected medications such as after approximately 3–4 under ECG monitoring aminophylline or nitrates 24 minutes. hours prior to the i.v. slowly injected under ECG monitoring) German Heart Institute Berlin & cmr-academy.com Table 3: Contraindications for dipyridamole / adenosine A gadolinium derivative is used (e.g. Gd- • Asthma or severe obstructive pulmonary 0.05 mmol/kg bodyweight injected with 4 ml per second. The bolus is followed by a 20 ml saline flush (infusion rate: 4 ml per second) to facilitate a compact bolus passage. We antagonists or cardiac glycosides (due to recommend the use of an automatic infusion system ( e.g. Medrad, Spectris MR injector) preparation and practice for rapid removal of the patient from the magnet needs to be practiced in addition to a close compliance with the termination criteria (Table 4). During stress examinations monitoring of the patient within the magnet is mandatory. The monitoring of blood pressure, cardiac rhythm and patients' symptoms can either examination requires the same precautions outside the scanner room connected to the patient with special extensions through a recommendations are listed in table 2. Apart waveguide in the radiofrequency cage, or by from the known specific contraindications using special CMR compatible equipment. A for MR, the drug related contraindications for adenosine and dipyridamole infusion are emergency treatment must be available at adenosine/dipyridamole stress MR imaging • persistent or symptomatic hypotension *When the Vector-ECG is used, pulse oximetry is not
Currently, only limited data is available regarding the accuracy of visual assessment and extensive experience is required to reach an acceptable standard. The alteration of the upslope of the myocardial response curve from stress to rest yields the highest difference between ischemic and normal myocardium. This parameter is superior to German Heart Institute Berlin & cmr-academy.com maximal signal intensity, which is mainly upslope of each myocardial segment by the intensity curve. Perfusion reserve index is results in improved visual assessment, but calculated by dividing the results of stress often renders semiquantification difficult. by the results at rest. This approach has yielded sensitivities and specificities of interpretation need to be taken into account: > 90% in selected patient populations. Its value in unselected patients remains to be wraparound) or misleadingly be interpreted (e.g. susceptibility) as perfusion deficits. Thus, training in MR image interpretation Table 5: Criteria for Visual Assessment of together with the interplay of the visual criteria given in table 5 will result in a sufficiently high diagnostic accuracy (own unpublished data showed: sensitivity 89%, • Signal -intensity Pattern & Location: initial passage of the contrast bolus are due subendocardial perfusion deficits difficult. Especially the trabeculae of the papillary muscles reaching into the left ventricular persistent over a few (2 to 10) dynamics cavity are washed with contrast agent and, epicardial border (epicardial "filling up" interpreted as regional ischemic perfusion Visual criteria for left ventricular myocardial perfusion deficits are given in table 5. • Myocardial Distribution of the Defect: Evaluate the equatorial slice first, then Semiquantification
check whether the suspected perfusion defect can be followed in corresponding semiquantification, as described briefly: the If a regional defect is found in the stress scan, but not in the rest scan, inducible diaphragmatic position due to breathing or diaphragmatic drift. Care needs to be taken lesion"). Regional persistence of the and to exclude the left ventricular cavity and the pericardium. The myocardium is then divided into 6 equiangular segments per slice and numbered clockwise beginning with the anterior septal insertion of the right Quantification
ventricle. An additional region of interest is placed within the cavity of the left ventricle excluding the myocardial segments and the prerequisites, not fully fulfilled with the papillary muscles. Images acquired after current contrast agents such as: linearity premature ventricular beats or insufficient between signal intensity and contrast agent cardiac triggering need to be excluded from concentration or adequate downslope. Most conditions. Signal intensity is determined for all dynamics and segments. The upslope of the resulting signal intensity time curve is image inhomogeneities, water exchange and determined by the use of a linear fit. To correct for possible differences of the input function, the results of the myocardial segments are corrected by dividing the German Heart Institute Berlin & cmr-academy.com To cover 16 segments we use 3 short axis apical segment (segment 17) is neglected Look at the images and check if the coil is "DSMR cookbook). A standardized way to reproducibly plan a short axis view can be found in the application guide. Define the plane on transversal slices parallel to the septum through the apex of the left ventricle and the coaptation point of which are all breathhold bFFE scans (scan duration ragning from 8 to 12 sec.), except for the multistack survey (bFFE, but free breathing patient) and the TFE-EPI perfusion Flip the orientation (90°) and adjust the plane on the first RAO through the apex and the middle of the mitral valve to get a second long axis view (nearly 4 chamber view). This slice orientation helps to prevent any angulation errors while planning the short axis views. (4) wall motion scan short axis (3 slices) Make use of the double-angulated image to define 3 slices perpendicular to the long axis of the heart representing the short axis geometry. The perfusion scan will be performed during stress and at rest (after an equlibration time Note: Under stress conditions even the normal heart experiences a change in its basal-to-apex dimensions ≥ 15 min after the first bolus injection). due to rotational deformation. To avoid visualization of the left ventricular outflow tract as well as to ensure sufficient imaging of the left ventricular cavity (esp. critical is the apical slice), we recommend to perform the planning on the endsystolic images: divide the distance from the apical epicardial border to the mitral valve plane in 5 equal parts. Then, distribute the 3 short It is of special importance to explain not only axes equally within the inner three-fifth of the distance the course of the examination to the patient but also the breathhold procedure. Generally the breathhold should be performed during endexpiration to ensure reproducible slice geometry. Plan the 4-chamber view on the equatorial short axis view, the stack should be aligned through the apex of the right ventricle and breathhold periods. The first is a short one (about 10-12 seconds, baseline acquisition of myocardial intensity), then the patient is asked to inhale and exhale once and hold Plan the 2-chamber view on the previously breath as long as possible. Before starting acquired 4-chamber view by just switching this breathhold-command the contrast bolus is administered. The patient should stop angulation (through the left ventricular apex and the coaptation point of the mitral valve). resulting in a fixed slice geometry during the first-pass of the contrast agent; in case the patient cannot hold his breath throughout the whole scan: ask the patient to inhale and orientation identical to the short axis cine previously acquired (scan 4). Wraparound has to be avoided carefully! We recommend Put venous line (≥ 18 gauge) in cubital vein to perform a TFE-EPI prior to the start of with two connections: one for adenosine, the adenosine infusion (e.g. 5 dynamics) with a breathhold command If necessary enlarge the field-of-view (results in decreasing Monitor blood pressure and heart frequency Repeat scan 7 at rest after ≥ 15 min delay. German Heart Institute Berlin & cmr-academy.com Flow chart 1: Adenosine Stress MR Perfusion Imaging (1) transversal(2) single-angulated view(3) double-angulated view German Heart Institute Berlin & cmr-academy.com German Heart Institute Berlin & cmr-academy.com German Heart Institute Berlin & cmr-academy.com German Heart Institute Berlin & cmr-academy.com TFE prepulse/before each shot/delay (ms) 1 (!!), (if not, adjust trigger delay !!!) German Heart Institute Berlin & cmr-academy.com This cookbook has been assembled from the knowledge available at the time of writing. The authors cannot take liability for dose regimen, infusion schemes, etc. If you find any errors or would like to suggest any improvements, please let us know at email@example.com or firstname.lastname@example.org. German Heart Institute Berlin & cmr-academy.com
Neutral Citation Number: 2013 EWHC 2125 (Ch) IN THE HIGH COURT OF JUSTICE CHANCERY DIVISION PROBATE In the estate of LOUISA ANN ASHKETTLE deceased Christopher Pymont QC - - - - - - - - - - - - - - - - - - - - - Between : (1) ROBERT MICHAEL ASHKETTLE Claimants (2) DENNIS ROBERT ASHKETTLE ROSALIND PATRICIA ANN GWINNETT Defendant - - - - - - - - - - - - - - - - -